Compound and a novel process for their preparation

ABSTRACT

The present invention is directed to a procedure for making an enantiomerically enriched compound containing a hydronaphthalene ring structure. The process involves reacting oxabenzonorbornadienes with nucleophiles using rhodium as a catalyst and in the presence of a phosphine ligand. The compounds synthesized may be used in pharmaceutical preparations for the treatment of a variety of diseases and conditions.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a division of U.S. application Ser. No.09/763,759, filed on Feb. 27, 2001. Now U.S. Pat. No. 6,525,068 U.S.Ser. No. 09/763,759 represents U.S. national phase of internationalapplication PCT/SE00/02090 with an international filing date of Oct. 26,2000 and which was published in English under Article 21(2) of the PCTon May 3, 2001. The international application claims priority to Swedishapplication 9903930-7, filed on Oct. 29, 1999.

FIELD OF THE INVENTION

The present invention is directed to methods for chemically synthesizingcompounds containing a hydronaphthalene ring structure. It encompassesthe compounds made by the methods, pharmaceutical preparationscontaining the compounds, and methods for treating patients using thesepharmaceutical preparations.

BACKGROUND OF THE INVENTION

The hydronaphthalene structure can be found in many natural products andpharmaceutical agents. These include homochelidonine (structure 1 below;Slavik, J.; et al., Collect. Czech. Chem. Commun. 30:3697 (1965); Spath,E., et al., Ber., 64:1123 (1931); Bersch, H. W., Arch. Pharm. (Weinheim,Ger.), 2914:91 (1958)) an alkaloid isolated from Chelidonium plants,dihydrexidine (structure 2 below; Snyder, S. E., J. Med. Chem., 38:2395(1995)) which shows antiparkinsonian character, etoposide (structure 3below; Kamal, A., et al., Tetrahedron Lett. 37:3359 (1996)) which isused in the treatment of various cancers, and SF-2315B (structure 4below; Kim, K., et al., J. Org. Chem. 60:6866 (1995)) which is a viralreverse transcriptase inhibitor. In addition, CNS agents,immunoregulatory agents and antibiotics contain variations on thisframework (Perrone, R., et al., J. Med. Chem. 38:942 (1995)).

Given the large number of pharmaceutically useful compounds whichcontain this core skeleton, new methodology which producesfunctionalized hydronaphthalene skeletons (structure 1) would clearly beof value.

Previous work on oxabicyclic ring opening reactions led to a catalyticenantioselective route to dihydronaphthol (Lautens, M., et al.,Tetrahedron 54:1107 (1998)) which was a key step in the total synthesisof sertraline (Lautens, M., et al, J. Org. Chem. 63:5276 (1997)).However, little is known about the ring opening of oxabenzonorbornadieneor similar compounds with the incorporation of nucleophiles during thering opening step. Duan and Chen developed a method of introducing arylgroups by using catalytic amounts of palladium (Duan, J.-P., et al.,Tetrahedron Lett., 34:4019 (1993); Duan, J.-P., et al., Organometallics14:1608 (1995)). Moinet et al., later developed an enantioselectiveversion of this reaction but the yields were low (Tetrahedron Lett.,36:2051 (1995)).

Catalytic organometallic processes that form carbon-heteroatom bonds arefar fewer in number than those which form carbon-carbon bonds. TheWacker Process (Henry, P. M., Paladium Catalysed Oxidation ofHydrocarbons, vol. 2, Reidel, Boston, (1980)), oxidative carbonylationsof amines and alcohols (Applied Homogeneous Catalysis withOrganometallic Compounds: A Comprehensive Handbook in Two Volumes (eds.:B. Cornils, W. A. Herrmann), VCH, New York, (1984)) and the formation ofarylamines and aryl ethers (Hartwig, J. F., Agnew. Chem. Int. Ed.37:2046 (1998); Widenhoefer, R. A., et al., J. Am. Chem. Soc. 119:6787(1997)) are a few that have been described to date.

SUMMARY OF THE INVENTION

The present invention is based upon the discovery of a rhodium catalyzedring opening reaction of oxabenzonorbornadienes or azabicyclic compoundsto produce a new carbon-oxygen bond via an intermolecular reaction withvarious alcohols. This reaction occurs in good yields with completeregio and diastereoselectivity and excellent enantioselectivity (e.g.,eq. 1).

In the reaction above, Z is O or NR_(a). This reaction will work whenoxabenzonorbornadienes or azabicyclic compounds are reacted withnitrogen nucleophiles, carboxylate nucleophiles, carbon nucleophiles orphenol nucleophiles. The invention encompasses not only the chemicalreactions but also the compounds made by the reactions and the use ofsuch compounds in the treatment of a variety of diseases and conditions.

In its first aspect, the invention is directed to a compound accordingto formula I:

in which R is selected from the group consisting of:

(a) H;

(b) a C₁-C₆ straight or branched alkyl;

(c) a straight or branched C₂-C₆ alkenyl;

(d) —(CH₂)_(n)R₁, wherein R₁ is a C₃-C₆ aryl, optionally substituted atone or more positions with a group selected from: Cl; F; NO₂; I; Br; aC₁-C₃ alkyl; and a C₁-C₃ alkoxy wherein n=0-3;

(e) —C(O)R₂, wherein R₂ is selected from the group consisting of: H;—(CH₂)_(n)R₁, wherein R₁ is as described above and n=0-3; and—(CH₂)_(n)C(O)R₃, wherein R₃ is a C₁-C₆ straight or branched alkyl andn=0-3;

(f) —C(O)(CH₂)_(p)—C(O)—O—R₄, wherein R₄ is a straight or branched C₁-C₆alkyl and wherein p=0-3;

(g) —R_(d)(CF₃)_(j), wherein R_(d) is a C₁-C₃ straight or branched alkyland j=1-3;

(h) —(CH₂)_(j)-TMS, wherein TMS is trimethylsilyl, and j=1-3;

X and Y are independently selected from the group consisting, of H; NH₂;F; Cl; Br; a C₁-C₃ alkyl; and a C₁-C₃ alkoxy;

or wherein the combination XY or YY together form a C₃-C₆ carbocyclicring or a C₃-C₆ heterocyclic ring containing one or more heteroatomsselected from the group consisting of: O; N; and S; and in which Z isselected from O or NR_(a), wherein R_(a) is selected from:

(i) phenyl;

(j) (O)C—O—R_(b), wherein R_(b) is a straight or branched C₁-C₆ alkyl;

(k) —SO₂—R_(c), wherein R_(c) is selected from the group consisting of:

i) C₁-C₆ straight or branched alkyl;

ii) —(CH₂)_(q)R_(e), wherein q=0-3 and R_(e) is a C₃-C₆ aryl, optionallysubstituted at one or more positions with a group selected from: Cl; F;NO₂; CN; I; Br; a straight or branched C₁-C₃ alkyl; a C₁-C₃ alkoxy; and—C(O)R_(f), wherein R_(f) is a C₁-C₃ alkyl; —(CH₂)_(r)CF₃, whereinr=0-3;

iii) —R_(g)(CF₃)_(s), wherein R_(g) is a C₁-C₃ straight or branchedalkyl and s=1-3;

iv) —(CH₂)_(s)-TMS, wherein TMS=trimethylsilyl and s=1-3;

(l) —SO₂—(CH₂)_(q)—Si(CH₃)₃ wherein q is 1-3.

Preferably, R in formula I is —(CH₂)_(n)R₁ and R₁ is a C₃-C₆ aryloptionally substituted at one or more positions with a group selectedfrom: Cl; F; NO₂; I; Br; a C₁-C₃ alkyl; and a C₁-C₃ alkoxy and whereinn=0-3. When Z is NR_(a), R_(a) is preferably phenyl; (O)C—O—C—(CH₃)₃;—SO₂—(CH₂)₂—Si(CH₃)₃; or —SO₂—R_(c), wherein R_(c) is —(CH₂)_(q)R_(e),wherein q=0-3 and R_(e) is a C₃-C₆ aryl, optionally substituted at oneor more positions with a group selected from: Cl; F; NO₂; CN; I; Br; astraight or branched C₁-C₃ alkyl; a C₁-C₃ alkoxy; and —C(O)R_(f),wherein R_(f) is a C₁-C₃ alkyl; —(CH₂)_(s)CF₃, wherein r=0-3.

The compounds of formula I described above may be prepared by reacting acompound of formula ROH with a compound of formula V:

in which R, X, Y, and Z are as defined above. The reaction is catalyzedby [Rh(COD)Cl]₂ in the presence of a phosphine ligand, preferablyselected from the group consisting of: DPPF; (R)-(S)-BPPFA; and(R)-(S)-PPF-P^(t)Bu₂. In prefered reactions: (a) the compound made is(1R*,2R*)-acetic acid 1-hydroxy-1,2-dihydro-naphthalen-2-yl ester andROH is acetic acid; (b) the compound made is (1R*,2R*)-propionic acid1-hydroxy-1,2-dihydro-naphthalen-2-yl ester and ROH is propionic acid;(c) the compound made is (1R,2R)-benzoic acid1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester and ROH is benzoic acid; (d)the compound made is (1R*,2R*)-formic acid1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester and ROH is formic acid; (e)the compound made is (1R*,2R*)-2-methyl acrylic acid1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester and ROH is methacrylic acid;(f) the compound made is (1R*,2R*)-malonic acid ethyl-ester(1-hydroxy-1,2-dihydro-naphthalen-2-yl) ester and ROH is ethyl malonicacid; and (g) the compound made is(1R,2R)-2-(4-bromo-phenoxy)-1,2-dihydro-naphthalen-1-ol and ROH isp-bromophenol; (h) the compound made isN-[(1R,2S)-2-methoxy-1,2-dihydrohydro-1-naphthalenyl]-4-methylbenzene-sulfonamideand ROH is MeOH; (i) the compound made is4-methyl-N-[(1R,2S)-2-phenoxy-1,2-dihydrohydro-1-naphthalenyl]benzenesulfonamideand the ROH is phenol; (j) the compound made is(1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2-dihydrohydro-2-naphthalenylacetate and the ROH is acetic acid; (k) the compound made is(1R,2S)-1-{[(4-methylphenyl)-sulfonyl]amino}-1,2-dihydro-2-naphthalenylbenzoate and the ROH is benzoic acid; (1) the compound made is(1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2-dihydro-2-naphthalenylpivalate and the ROH is pivalic acid; (m) the compound made isN-[(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenyl]-2-(trimethylsilyl)ethanesulfonamideand ROH is methanol.

In a second aspect the invention is directed to a compound according toformula II:

in which R is selected from the group consisting of:

(a) a C₁-C₆ straight or branched alkyl;

(b) —(CH₂)_(q)R₅, wherein q=0-3 and R₅ is a C₃-C₆ aryl optionallysubstituted at one or more positions with a group selected from: astraight or branched C₁-C₃ alkyl; a C₁-C₃ alkoxy; Br; I; Cl; CN; F; NO₂;—(CH₂)_(r)CF₃, wherein r=0-3; and —C(O)R₆, wherein R₆, is a C₁-C₃ alkyl;

(c) —R₇(CF₃)₅, wherein R₇ is a C₁-C₃ straight or branched alkyl ands=1-3;

(d) —(CH₂)_(s)-TMS, wherein TMS=trimethylsilyl and s=1-3;

X and Y are independently selected from the group consisting of H; NH₂;F; Cl; Br; a C₁-C₃ alkyl; and a C₁-C₃ alkoxy;

or wherein the combination XY or YY together form a C₃-C₆ carbocyclicring or a C₃-C₆ heterocyclic ring containing one or more heteroatomsselected from the group consisting of: O; N; and S; and

in which Z is selected from O or NR_(a), wherein R_(a) is selected from:

(e) phenyl;

(f). (O)C—O—R_(b), wherein R_(b) is a straight or branched C₁-C₆ alkyl;

(g) —SO₂—R_(c), wherein R_(c) is selected from the group consisting of:

i) C₁-C₆ straight or branched alkyl;

ii) —(CH₂)_(q)R_(e), wherein q=0-3 and R_(e) is a C₃-C₆ aryl, optionallysubstituted at one or more positions with a group selected from: Cl; F;NO₂; CN; I; Br; a straight or branched C₁-C₃ alkyl; a C₁-C₃ alkoxy; and—C(O)R_(f), wherein R_(f) is a C₁-C₃ alkyl; —(CH₂)_(r)CF₃, whereinr=0-3;

iii) —R_(g)(CF₃)_(s), wherein R_(g) is a C₁-C₃ straight or branchedalkyl and s=1-3;

iv) —(CH₂)_(s)-TMS, wherein TMS=trimethylsilyl and s=1-3;

(h) —SO₂—(CH₂)_(q)—Si(CH₃)₃ wherein q is 1-3.

Preferably, R in formula II is —(CH₂)_(q)R₅ wherein q=0-3 and R₅ is aC₃-C₆ aryl optionally substituted at one or more positions with a groupselected from: a straight or branched C₁-C₃ alkyl; a C₁-C₃ alkoxy; I;Cl; CN; F; NO₂; —(CH₂)_(r)CF₃, wherein r=0-3; and —C(O)R₆, wherein R₆ isa C₁-C₃ alkyl.

The compounds of formula II described above may be prepared by reactinga compound of formula ROH with a compound of formula V:

wherein R, X, Y, and Z are as defined above in connection with formulaII and in which the reaction is catalyzed by [Rh(COD)Cl]₂ in thepresence of a phosphine ligand, preferably (S)-(R)-PPF-P^(t)Bu₂. Inpreferred reactions: (a) the compound made is(1S,2S)-2-methoxy-1,2-dihydro-naphthalen-1-ol, and ROH is methanol; (b)the compound made is (1S,2S)-2-(ethoxy)-1,2-dihydro-naphthalen-1-ol, andROH is ethanol; (c) the compound made is(1S,2S)-2-isopropoxy)-1,2-dihydro-naphthalen-1-ol and ROH isisopropanol; (d) the compound made is(1S,2S)-2-1-propenyloxy)-1,2-dihydro-naphthalen-1-ol, and ROH is allylalcohol; (e) the compound made is(1S,2S)-2-(2-trimethylsilyl-ethoxy)-1,2-dihydro-naphthalen-1-ol, and ROHis trimethylsilyl-ethanol; (f) the compound made is(1S,2S)-2-benzyloxy-1,2-dihydro-naphthalen-1-ol, and ROH isbenzylalcohol; (g) the compound made is(1S,2S)-2-4-methoxybenzyloxy-1,2-dihydro-naphthalen-1-ol, and ROH isanisylalcohol; (h) the compound made is(1S,2S)-2-(2,2,2-trifluoro-ethoxy)-1,2-dihydro-naphthalen-1-ol, and ROHis trifluoroethanol; (i) the compound made is(1S,2S)-2-(2,2,2-trifluoro-1-trifluoromethyl-ethoxy)-1,2-dihydro-naphthalen-1-oland ROH is hexafluoro-isopropanol; (j) the compound made is(1S,2S)-6,7-difluoro-2-methoxy-1,2-dihydro-naphthalen-1-ol and ROH ismethanol; (k) the compound made is(1S,2S)-6-methoxy-5,6-dihydro-naphtho[2,3-d][1,3]dioxol-5-ol and ROH ismethanol; (1) the compound made is(1S,2S)-6,7-dibromo-2-methoxy-5,8-dimethyl-1,2-dihydro-naphthalen-1-oland ROH is methanol; (m) the compound made is(1S,2S)-2-phenoxy-1,2-dihydro-naphthalen-1-ol and ROH is phenol; (n) thecompound made is (1S,2S)-2-(4-nitrophenoxy)-1,2-dihydro-naphthalen-1-oland ROH is 4-nitrophenol; (O) the compound made is(1S,2S)-2-(4-cyanophenoxy)-1,2-dihydro-naphthalen-1-ol and ROH is4-cyanophenol; (p) the compound made is(1S,2S)-2-(4-acylphenoxy)-1,2,-dihydro-naphthalen-1-ol and ROH is4-hydroxyaceto-phenone; (q) the compound made is(1S,2S)-2-(4-trifluoromethylphenoxy)-1,2,-dihydro-naphthalen-1-ol andROH is 4-trifluoromethylphenyl; (r) the compound made is(1S,2S)-2-(4-fluorophenoxy)-1,2-dihydro-naphthalen-1-ol and ROH is4-fluorophenol; (s) the compound made is(1S,2S)-2-(4-chlorophenoxy)-1,2-dihydro-naphthalen-1-ol and ROH is4-chlorophenol; (t) the compound made is(1S,2S)-2-(4-iodophenoxy)-1,2-dihydro-naphthalen-1-ol and ROH is4-iodophenol; (u) the compound made is(1S,2S)-2-(4-methylphenoxy)-1,2-dihydro-naphthalen-1-ol and ROH isp-cresol; (v) the compound made is(1S,2S)-2-(4-methoxyphenoxy)-1,2-dihydro-naphthalen-1-ol and ROH is4-methoxyphenol; and (w) the compound made is(1S,2S)-2-(2-bromophenoxy)-1,2-dihydro-naphthalen-1-ol and ROH is2-bromophenol. When Z is NR_(a), R_(a) is preferably phenyl;(O)C—O—C—(CH₃)₃;

or (O)S(O)—(CH₂)₂—Si(CH₃)₃.

The invention is also directed to a compound according to formula III:

wherein TBDMSO is a tert-butyldimethylsiloxy group, and R, X, and Y areas defined in above in connection with formula I. These compounds may bemade by preparing a compound of formula I according to the processdescribed above and then reacting the compound formed with a salt oftert-butyldimethylsilylic acid. Preferably, the compound formed is(1R*,2R*)-malonic acid(1-tert-butyldimethylsiloxy-1,2-dihydro-naphthalen-2-yl) ester ethylester and ROH is tert-butyldimethylsilylic acid.

In another aspect, the invention is directed to a compound according toformula IV:

a) in which R₈ is H or CH₃;

b) t=0-3

c) R₉ is a C₃-C₆ aryl optionally substituted at one or more positionswith a group selected from: a C₁-C₃ alkyl; a C₁-C₃ alkoxy; Cl; F; NO₂;and CF₃;

or R₉ together with N form a ring structure selected from: a phthalamidering; a pyrrolidine ring; a piperidine ring; a tetrahydroquinoline ring;and an indole ring; said ring structure being optionally substituted atone or more positions with a group selected from: a C₁-C₃ alkyl; a C₁-C₃alkoxy; Cl; F; NO₂; and CF₃;

d) X and Y are independently selected from the group consisting of H;NH₂; F; Cl; Br; a C₁-C₃ alkyl; and a C₁-C₃ alkoxy; or wherein thecombination XY or YY together form a C₃-C₆ carbocyclic ring or a C₃-C₆heterocyclic ring containing one or more heteroatoms selected from thegroup consisting of: O; N; and S;

e) Z is selected from O or NR_(a), wherein R_(a) is selected from:

(i) a straight or branched C₁-C₆ alkyl;

(ii) phenyl;

(iii) (O)C—O—R_(b), wherein R_(b) is a straight or branched C₁-C₆ alkyl;

(iv) —SO₂—R_(c), wherein R_(c) is an unsubstituted phenyl or a phenylsubstituted with a C₁-C₃ alkyl or NO₂; and

(v) —SO₂—(CH₂)_(q)—Si(CH₃)₃ wherein q is 1-3; and

f) when Z is O, R₁₀ is H; when Z is NR_(a), R₁₀ is either H or CH₃.

Preferably, R₈ in formula IV is H and R₉ together with N form a ringselected from the group consisting of a phthalamide ring; a pyrrolidinering; a piperidine ring; a tetrahydroquinoline ring; and an indole ring;the ring being optionally substituted at one or more positions with agroup selected from: a C₁-C₃ alkyl; a C₁-C₃ alkoxy; Cl; F; NO₂; and CF₃.When Z is NR_(a), R_(a) is preferably methyl;

The compounds of formula IV described above may be prepared by reactinga compound of formula R₉—(CH₂)_(t)NHR₈ with a compound of formula V

in which R₈, R₉, t, X, Y, and Z are as defined above in connection withcompounds of formula IV and the reaction is catalyzed by [Rh(COD)Cl]₂ inthe presence of a phosphine ligand; preferably selected from the groupconsisting of: DPPF; (R)-(S)-BPPFA; and (R)-(S)-PPF-P^(t)Bu₂. When Z isNR_(a), the reaction will produce a product in which R₁₀ is H. Asubsequent reaction may be used to convert R₁₀ to a methyl as set forthin the Examples section below. Most typically, the process will be usedto produce products in which R₉ together with N form a ring selectedfrom the group consisting of: a phthalamide ring; a pyrrolidine ring; apiperidine ring; a tetrahydroquinoline ring; and an indole ring; saidring structures being optionally substituted at one or more positionswith a group selected from: a C₁-C₃ alkyl; a C₁-C₃ alkoxy; Cl; F; NO₂;and CF₃. In preferred reactions: (a) the compound made is(1R,2R)-2-(1-hydroxy-1,2-dihydro-naphthalen-2-yl) isoindole-1,3-dioneand R₉—(CH₂)_(s)NHR₈ is phthalimide; (b) the compound made is(1R*,2R*)-2-pyrrolidin-1-yl-1,2-dihydro-naphthalen-1-ol andR₉—(CH₂)₅NHR₈ is pyrrolidine; (c) the compound made is (1R*,2R*)-2-piperidin-1-yl-1,2-dihydro-naphthalen-1-ol andR₉—(CH₂)_(s)NHR₈ is piperidine; (d) the compound made is(1R,2R)-2-(3,4-dihydro-2H-quinolin-1-yl)-1,2-dihydro-naphthalen-1-ol andR₉—(CH₂)_(s)NHR₈ is tetrahydroisoquin-oline; (e) the compound made is(1R,2R)-2(methyl-phenyl-amino)-1,2-dihydro-naphthalen-1-ol andR₉—(CH₂)_(s)NHR₈ is N-methylaniline; (f) the compound made is(1R*,2R*)-2-benzylamino-1,2-dihydro-naphthalen-1-ol and R₉—(CH₂)_(s)NHR₈is benzyl-amine; (g) the compound made is(1R*,2R*)-2-(4-methoxy-benzylamino)-1,2-dihydro-naphthalen-1-ol andR₉—(CH₂)_(s)NHR₈ is p-methoxybenzylamine; and (h) the compound made is(1R,2R)-2-indol-1-yl-1,2-dihydro-naphthalen-1-ol and R₉—(CH₂)_(s)NHR₈ isindole; (i) the compound made isN-[1R,2R)-2(1-pyrrolidinyl)-1,2-dihydronaphthalenyl]-4-methylbenzenesulfonamideand the R₉—(CH₂)_(t)NHR₈ is pyrrolidine; (j) the compound made isN-[(1R,2S)-2-(1H-indol-1-yl)-1,2-dihydro-1-naphthalenyl]-4-methylbenzenesulfonamideand the R₉—(CH₂)_(t)NHR₈ is indole; (k) the compound made isN-[(1R,2S)-2-(3,4-dihydro-2(1H)-isoquinolinyl)-1,2-dihydro-1-naphthalenyl]-4-methylbenzenesulfonamideand the R₉—(CH₂)_(t)NHR₈ is tetrahydroisoquinoline; (1) the compoundmade isN-[(1R,2S)-2-(3,4-dihydro-1(2H)-quinolinyl)-1,2-dihydro-1-naphthalenyl]-4-methylbenzenesulfonamideand the R₉—(CH₂)_(t)NHR₈ is tetrahydroquinoline; (m) the compound madeis4-methyl-N-[(1R,2S)-2-(1-piperidinyl)-1,2-dihydro-1-naphthalenyl]-benzenesulfonamideand the R₉—(CH₂)_(t)NHR₈ is piperidine.

The invention also encompasses seven other processes. In the first(1S,2S)-N-(1-hydroxy-1,2-dihydro-naphthalen-2-yl)-benzene sulfonamide isformed by reacting oxabenzonorbornadiene with benzenesulfonamide. In thesecond, (1S*,2R*)-2-(hydroxy-1,2-dihydro-naphthalen-2-yl)malonic aciddimethyl ester is formed by reacting oxabenzonorbornadiene with dimethylmalonate. Both reactions are catalyzed by [Rh(COD)Cl]₂ in the presenceof a phosphine ligand. In the third, the compound of formula VI isformed by reacting a compound of formula IV, which is produced asdescribed above in connection with formation of compounds of formula IV,with iodomethane. In preferred reactions, the compound made isN,4-dimethyl-N-[(1R,2S)-2-(1-pyrrolidinyl)-1,2-dihydro-1-naphthalenyl]benzenesulfonamide.In the fourth, the compound of formula VII is formed by reactingcompound of formula VI with hydrogen in the presence of palladiumcatalyst. The compound made isN,4-dimethyl-N-[(1R,2S)-2-(1-pyrrolidinyl)-1,2,3,4-tetrahydro-1-naphthalenyl]benzenesulfonamide.In the fifth, the compound of formula VIII is formed by reacting thecompound of formula VII with sodium borohydride. The compound made usingthis reaction is(1R,2S)-N-methyl-2-(1-pyrrolidinyl)-1,2,3,4-tetrahydro-1-naphthalenamine.In the sixth, the compound of formula IX is formed by reacting acompound of formula IV which is produced as described above inconnection with formation of compounds of formula IV, with iodomethane.The compound made using this reaction isN-methyl-4-nitro-N-[(1R,2S)-2-(1-pyrrolidinyl)-1,2-dihydro-1-naphthalenyl]benzenesulfonamide.In the seventh, the compound of formula X is formed by reacting acompound of formula I which is produced as described above in connectionwith formation of compounds of formula I, with iodomethane. The compoundmade using this reaction is(1R,2S)-1-{methyl[(4-methylphenyl)sulfonyl]amino}-1,2-dihydro-2-naphthalenylacetate.

Overall, the most preferred compounds of the invention are:

a) (1S,2S)-2-methoxy-1,2-dihydro-naphthalen-1-ol;

b) (1S,2S)-2-(ethoxy)-1,2-dihydro-naphthalen-1-ol;

c) (1S,2S)-2-(isopropoxy)-1,2-dihydro-naphthalen-1-ol;

d) (1S,2S)-2-(1-propenyloxy)-1,2-dihydro-naphthalen-1-ol;

e) (1S,2S)-2-(2-trimethylsilyl-ethoxy) 1,2-dihydro-naphthalen-1-ol;

f) (1S,2S)-2-benzyloxy-1,2-dihydro-naphthalen-1-ol;

g) (1S,2S)-2-(4-methoxybenzyloxy)-1,2-dihydro-naphthalen-1-ol;

h) (1S,2S)-2-(2,2,2-trifluoro-ethoxy)-1,2-dihydro-naphthalen-1-ol;

i)(1S,2S)-2-(2,2,2-trifluoro-1-trifluoromethyl-ethoxy)-1,2-dihydro-naphthalen-1-ol;

j) (1S,2S)-6,7-difluoro-2-methoxy-1,2-dihydro-naphthalen-1-ol;

k) (1S,2S)-6-methoxy-5,6-dihydro-naphthol[2,3-d][1,3]dioxol-5-ol;

l)(1S,2S)-6,7-dibromo-2-methoxy-5,8-dimethyl-1,2-dihydro-naphthalen-1-ol;

m) (1R*,2R*)-acetic acid 1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester;

n) (1R*,2R*)-propionic acid 1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester;

o) (1R,2R)-benzoic acid 1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester;

p) (1R*,2R*)-formic acid 1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester;

q) (1R*,2R*)-2-methyl acrylic acid1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester;

r) (1R*,2R*)-malonic acid ethyl ester(1-hydroxy-1,2-dihydro-naphthalen-2-yl) ester;

s) (1R*,2R*)-malonic acid(1-tert-butylbimethylsiloxy-1,2-dihydro-naphthalen-2-yl) ethyl ester;

t) (1S*,2S*)₄-tert-butyldimethylsiloxy-1,4-dihydro-naphthalen-2-yl)acetic acid ethyl ester;

u)(1R,2R)-2-(1-hydroxy-1,2-dihydro-naphthalen-2-yl)-isoindole-1,3-dione;

v) (1S,2S)-N-(1-hydroxy-1,2-dihydro-naphthalen-2-yl)-benzenesulfonamide;

w) (1R*,2R*)-9-pyrrolidin-1-yl-1,2-dihydro-naphthalen-1-ol;

x) (1R*,2R*)-2-piperidin-1-yl-1,2-dihydro-naphthalen-1-ol; y)(1R,2R)-2-(3,4-dihydro-2H-quinolin-1-yl)-1,2-dihydro-naphthalen-1-ol;

z) (1R,2R)-2-(methyl-phenyl-amino)-1,2-dihydro-naphthalen-1-ol;

aa) (1R*,2R*)-2-benzylamino-1,2-dihydro-naphthalen-1-ol;

bb) (1R*,2R*)-2-(4-methoxy-benzylamino)-1,2-dihydro-naphthalen-1-ol;

cc) (1R,2R)-2-indol-1-yl-1,2-dihydro-naphthalen-1-ol;

dd) (1S*,2R*)-2-(hydroxy-1,2-dihydro-naphthalen-2-yl)malonic aciddimethyl ester;

ee) (1S,2S)-2-phenoxy-1,2-dihydro-naphthalen-1-ol;

ff) (1S,2S)-2-(4-nitrophenoxy)-1,2-dihydro-naphthalen-1-ol;

gg) (1S,2S)-2-(4-cyanophenoxy)-1,2-dihydro-naphthalen-1-ol;

hh) (1S,2S)-2-(4-acylphenoxy)-1,2-dihydro-naphthalen-1-ol;

ii) (1S,2S)-2-(4-trifluoromethylphenoxy)-1,2-dihydro-naphthalen-1-ol;

jj) (1S,2S)-2-(4-fluorophenoxy)-1,2-dihydro-naphthalen-1-ol;

kk) (1S,2S)-2-(4-chlorophenoxy)-1,2-dihydro-naphthalen-1-ol;

ll) (1S,2S)-2-(4-iodophenoxy)-1,2-dihydro-naphthalen-1-ol;

mm) (1R,2R)-2-(4-bromo-phenoxy)-1,2-dihydro-naphthalen-1-ol;

nn) (1S,2S)-2-(4-methylphenoxy)-1,2-dihydro-naphthalen-1-ol;

oo) (1S,2S)-2-(4-methoxyphenoxy)-1,2-dihydro-naphthalen-1-ol;

pp) (1S,2S)-2-(2-bromophenoxy)-1,2-dihydro-naphthalen-1-ol;

qq)4-methyl-N-[(1R,2S)-2-(1-piperidinyl)-1,2-dihydro-1-naphthalenyl]benzenesulfonamide;

rr) N-[(1R,2S)-2-(3,4-dihydro-1(2H)-quinolinyl)-1,2-dihydro-1-naphthalenyl]-4-methylbenzenesulfonamide;

ss) N-[(1R,2S)-2-(3,4-dihydro-2(1h)-isoquinolinyl)-1,2-dihydro-1-naphthalenyl]-4-methylbenzenesulfonamide;

tt)N-[(1R,2S)-2-(1H-indol-1-yl)-1,2-dihydro-1-naphthalenyl]-4-methylbenzenesulfonaminde;

uu) (1R,2S)-2-methoxy-N-phenyl-1,2-dihydro-1-naphthalenamine;

vv) tert-butyl (1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenylcarbamate;

ww)N-[(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenyl]-2-(trimethylsilyl)ethanesulfonamide;

xx)N,4-dimethyl-N-[(1R,2S)-2-(1-pyrrolidinyl)-1,2,3,4-tetrahydro-1-naphthalenyl]-benzenesulfonamide;

yy)N,4-dimethyl-N-[(1R,2S)-2-(1-pyrrolidinyl)-1,2-dihydro-1-naphthalenyl]-benzenesulfonamide;

zz)N-hydroxy-4-({methyl[(1R,2S)-2-(1-pyrrolidinyl)-1,2-dihydro-1-naphthalenyl]amino}sulfonyl)-N-oxobenzenaminium;

aaa)N-methyl-4-nitro-N-[(1R,2S)-2-(1-pyrrolidinyl)-1,2-dihydro-1-naphthalenyl]-benzenesulfonamide;

bbb)(1R,2S)-N-methyl-2-(1-pyrrolidinyl)-1,2,3,4-tetrahydro-1-naphthalenamine;

ccc)N-[(1R,2S)-2-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl]-4-methylbenzenesulfonamide;

ddd)N-[(1R,2S)-2-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl]-4-methylbenzenesulfonamide;

eee)4-methyl-N-[(1R,2S)-2-phenoxy-1,2,3,4-tetrahydro-1-naphthalenyl]benzenesulfonamide;

fff)(1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2,3,4-tetrahydro-2-naphthalenylacetate;

ggg)(1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2-dihydro-2-naphthalenylbenzoate;

hhh)(1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2-dihydro-2-naphthalenylpivalate;

iii)N-[(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenyl]-2-(trimethylsilyl)ethanesulfonamide;

jjj) tert-butyl (1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenylcarbamate;and

kkk)4-nitro-N-[(1R,2S)-2-(1-pyrrolidinyl)-1,2-dihydro-1-naphthalenyl]benzenesulfonamide.

Any of the compounds described above may be incorporated into apharmaceutical preparation and administered to a patient in an amounteffect for relieving one or more symptoms associated with a variety ofdiseases and conditions. Among the diseases that may be treated areParkinson's disease, cancer and AIDS.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is based upon the discovery of a new process forthe formation of enantiomerically enriched compounds containing thehydronaphthalene ring structure. The process involves reacting an aza-or oxabenzonorbornadiene compound with a nucleophile in the presence ofa rhodium catalyst and a phosphine ligand. Detailed procedures for theformation of precursor compounds and their use in reactions are setforth in the Examples section below. Preferred nucleophiles arealcohols, phenols, amines, and stabilized carbanions such as malonatesand malonate equivalents. In cases where simple aliphatic amines areused, reactions should be performed in the presence of a tertiary aminehydrochloride. This is not necessary for other types of amines. Whencarboxylic acids are used, reactions should be carried out in thepresence of a tertiary amine, e.g., triethylamine. Alternatively, thesodium or potassium salt of the carboxylic acid may be reacted in thepresence of the hyrochloride of a tertiary amine, e.g. in the presenceof triethylamine hydrochloride. It has been found that carboxylatering-opened products can be made to undergo a subsequent transformationto produce 1,4-disubstituted dihyronaphthalenes. This is accomplished byan S_(N)2′ addition of nucleophiles under catalytic or non-catalyticconditions to the allyl acetate functionality. For an example of theconversion of (1R*,2R*)-Malonic acid(1-tert-butyldimethylsiloxy-1,2-dihydro-naphthalen-2-yl) ester ethylester to(1S*,2S*)-(4-Tert-butyldimethylsiloxy-1,4-dihydro-naphthalen-2-yl)acetic acid ethyl ester see the Examples section below.

The preferred catalyst is [Rh(COD)Cl]₂ and, depending upon theparticular product desired, preferred ligands are DPPF or a chiralanalogs of DPPF, (R)-(S)-BPPFA; (R)-(S)-PPF-P^(t)Bu₂ and(S)-(R)-PPF-P^(t)Bu₂. The ligands may be prepared by any processdescribed in the literature (see, e.g., Toni et al., J. Am. Chem. Soc.116:4062 (1994)). Reactions may be carried out using trifluoroethanol(TEE) or tetrahydrofuran (THE) as solvents under an inert atmosphere,preferably of nitrogen. The reaction temperature should typically be atleast 60° C. and preferably about 80° C.

The compounds formed may be incorporated into a pharmaceuticalcomposition and used in the treatment of a variety of diseases andconditions. Specifically, the compounds may be used in the treatment ofParkinson's disease, cancers, and AIDS. The total daily dosage ofcompound administered to a patient should be at least the amountrequired to reduce or eliminate one or more symptoms associated with thecondition being treated. For example, in the treatment of Parkinson'sdisease, sufficient agent should be administered to reduce the severityor frequency of tremors or other movement disorders associated with thedisease. In treating cancers, agents should typically be given at adosage sufficient to reduce tumor size or at a dosage sufficient toreduce the total number of cancerous cells in a patient. The actual doseselected for an individual patient will be determined by the attendingphysician based upon clinical conditions and using methods well known inthe art. Agents may be provided in either a single or multiple dosageregimen, e.g., a patient may be administered compounds twice a day.

Any route of administration and dosage form is compatible with thepresent invention, and therapeutic agents may be administered as eitherthe sole active ingredient or in combination with other therapeuticallyactive drugs. Routes of delivery compatible with the invention includeparenteral, per oral, internal, pulmonary, rectal, nasal, vaginal,lingual, transdermal, intravenous, intra arterial, intramuscular,intraperitoneal, intra cutaneous, and subcutaneous routes. Specificdosage forms that may be used include tablets, pills, capsules, powders,aerosols, suppositories, skin patches, parenteral, and oral liquids,including oil aqueous suspensions, solutions, and emulsions. Sustainedrelease dosage forms may also be used. All dosage forms may be preparedusing methods that are standard in the art (see, e.g., Reaming'sPharmaceutical Sciences, 16^(the) ed., A. Oslo, editor, Easton Pa.(1980)).

Therapeutic agents may be used in conjunction with any of the vehiclesand excipients nly employed in pharmaceutical preparations, e.g., talc,gum arabic, lactose, starch, magnesium stearate, cocoa butter, aqueousor non-aqueous solvents, oils, paraffin derivatives, glycols, etc.Coloring and flavoring agents may also be added to preparations designedfor oral administration. Solutions can be prepared using water orphysiologically compatible organic solvents such as ethanol,1,2-propylene glycol, polyglycols, dimethyl sulfoxide, fatty alcohols,triglycerides, partial esthers of glycerine, and the like. Parenteralcompositions containing compounds may be prepared using conventionaltechniques and include sterile isotonic saline, water, 1,3-butane diol,ethanol, 1,2-propylene glycol, polyglycols mixed with water, Ringer'ssolution, etc.

If desired, a patient may be initially given a relatively low dose oftherapeutic agent in order to determine whether any adverse side effectsare experienced. This may be particularly important in cases where apatient is taking other medications or has clinical characteristics thatsuggest that they may not be able to tolerate high drug dosages. Ifadverse side effects are not experienced by a patient, dosage may begradually increased until a satisfactory alleviation of symptoms isachieved. For example, the dosage given to a patient with AIDS may beincreased until blood counts return to a normal or more normal level.

EXAMPLES

I. Compounds Made Using Oxabenzonorbornadienes

Example 1 Rhodium Catalysed Synthesis of Enatiomerically Enrichedtrans-2-Alkoxy-1,2-dihydro-naphthalen-1-ols

In 1973, Hogeveen and Middelkoop reported a [Rh(CO)₂Cl]₂ catalyzed ringopening reaction of 5 by reaction with methanol giving 6. (Hogeveen, H.,et al., Tetrahedron Lett. 190:1 (1973)) Subsequently, Ashworth andBerchtold reported the stereochemistry of this reaction to be cis asshown after the formation of a Diels-Alder adduct with 9 (scheme 1)(Ashworth, R. W., et al., Tetrehedron Lett. 339 (1977)). Thisstereochemistry is in keeping with the observation of exo attack bynucleophiles with other oxabicyclic starting materials (Lautens, M.,Synlett 179 (1993)). Hogeveen and Middelkoop also reported that thereaction was regioselective when only one of the bridgehead positionswas substituted, that is 11 gave only regioisomer 12.

When 13 (Stiles, M., e al., J. Am. Chem. Soc. 82:3802 (1960)) wassubjected to the Hogeveen and Middelkoop conditions, no reaction wasobserved. However, by changing the solvent system to a 1:1 mixture oftrifluoroethanol (TFE):methanol and by increasing the temperature to 60°C., the desired product 14 was isolated in 70% yield. Remarkably, thestereochemistry of 14 was trans as proven by comparison with authenticsamples of both stereoisomers of dimethoxytetrahydronaphthalene 15 (eq.2) (The cis isomer of 15 was prepared by reaction of1,2-dihydronaphthalene with OSO₄ followed by methylation withdimethylsulfate (DMS). The trans isomer was prepared by epoxidation of1,2-dihydronaphthalene followed by ring opening with hyroxide anddimethylation with DMS).

Given the ability of this reaction to set tip two stereocentres withcomplete regio and stereocontrol, the possibility of rendering itasymmetric was investigated. A serious drawback of the existing catalyst[Ph(CO)₂Cl]₂, however, was that the addition of phosphine ligandscompletely inhibited the reaction. By changing to a rhodium sourcepossessing the more labile COD ligand, [Rh(COD)Cl]₂, it was possible toexamine the catalytic ability of several chiral phosphine ligands. Notall rhodium-ligand combinations performed equally well. DPPE and BINAPdid not produce the desired product, and phosphites resulted in pooryields. DPPF was very efficient, however, giving 14 in 88% yield. Oneadvantage of DPPF is that a number of chiral analogues have beenprepared and could be studied to determine enantioselectivity. JOSIPHOSligands (Togni, A., et al., J. Am. Chem. Soc. 116:4062 (1994)) wereamong the chiral ligands examined which gave the most promising results.For example, PPF-P^(t)Bu₂ 16 gave 14 in 84% yield and 86% ee at 60° C.The ee could be significantly improved to 97% when the reactiontemperature was increased by 20° C.

These reactions were typically run as a 1:1 mixture of MeOH:TFE under anitrogen atmosphere which gave 13 accompanied by small amounts ofnaphthol. In neat trifluoroethanol under a nitrogen atmosphere, naphtholis the major product with less than 5% conversion to thetrifluoroethanol ring-opened product. Remarkably, this is not the casewhen the reaction is run under a carbon monoxide atmosphere. In thepresence of CO, the reaction with neat TFE gives the TFE ring-openedproduct 17 in 70% yield after 3 hours. A colour change of the solution,from yellow to red was observed, suggesting that the CO was interactingwith the rhodium metal. When the reaction was performed under asymmetricconditions using PPF-P^(t)Bu₂, 17 was obtained in 70% yield and 98% eeindicating that the ligand remains bound to the metal even if CO bindinghas occurred (table 1).

TABLE 1 Effects of Solvent and Atmosphere

Atmosphere Solvent/Equiv. TFE Yield 19 ee N₂ TFE/neat  0%* CO TFE/neat70% 98% N₂ THF/5 eq. TFE 70% 98% *only product observed is naphthol

Reactions run in alcohols other that TFE proceeded at a much slowerrate. When the solvent was changed to THF, the reaction worked equallywell with a broad range of alcohols under racemic and enantioselectiveconditions, and only five equivalents of the alcohol were required. THFalso allowed the use of very low catalyst loadings, typically in therange of 0.125 mmol % of [Rh(COD)Cl]₂ and 0.25 mol % of 16. While TFEwould only add to give 17 when the reaction was run under a COatmosphere in neat TFE, this was not the case in THF. When THF was usedas the solvent, TFE added efficiently under an inert nitrogen atmosphereto give 17 in 70% yield and 98% ee. Even the very weakly nucleophilichexafluoroisopropanol (HFI) added under these reaction conditions togive 23 in 90% yield and 93% ee (table 2).

TABLE 2 Rhodium Catalysed Ring Opening of 12 with Various Alcohols

ROH Product Yield(%) ee(%)^(b) MeOH^(a) 14 96 97 EtOH^(a) 16 84 97^(i)PrOH^(a) 18 94 93 Allyl Alcohol 19 92 >99 TMS Ethanol^(a) 20 53 95Benzyl Alcohol 21 66 >98 p-Methoxybenzyl Alcohol 22 87 97 TFE 17 70 98HFI 23 90 93 ^(a)These reactions were performed under unoptimisedconditions using 10 eq ROH ^(b)ee determined by formation of Moshersester or by HPLC analysis with a Chiralcel OD Column

In order to investigate the effects of substituents on the aromatic ringof 13, difluoro (24), methylenedioxy (25), and dimethyldibromo (26)substrates were prepared (Hart, H., Tetrahedron 43:5203 (1987)) andreacted them under the standard conditions. All gave the correspondingring opened products in good yields and excellent ee's (chart 1)indicating that this reaction is not sensitive to remote substitution orelectronic effects on the aromatic ring.

Example 2 Formation of 1,4-epoxy-1,4-dihydronaphthanlene (13)

To furan (100 ml, 1.37 ml) in DME (100 ml) at 50° C. in a flame driedthree neck flask with a reflux condenser and two addition funnelsattached was added simultaneously over two hours a solution ofanthranilic acid (27.5 g, 200 mmol) in DME (100 ml) and a separatesolution of isoamylnitrite (40 mL, 298 mmol) in DME (50 mL). Uponcompletion of addition, the reaction was allowed to stir at 50° C. for30 min until no further gas was evolved. The reaction mixture was thencooled to room temperature and portioned between Et₂O and saturatedK₂CO₃ and the aqueous layer was extracted three times with Et₂O. Thecombined organic layer were washed with brine, dried over MgSO₄ andconcentrated. Bulb to bulb distillation gave 13 (18.5 g, 64%) as a whitesolid. The spectral data correspond well with the literature data.¹⁷

Example 3 Compounds Formed by Reactions Involving Alcohols

(1S,2S)-2-Methoxy-1,2-dihydro-naphthalen-1-ol (14) To a flame driedround bottom flask, [Rh(COD)Cl]₂ (0.5 mg, 0.0009 mmol),(R)-(S)-PPF-P^(t)Bu₂ (1.0 mg, 0.0018 mmol) and 13 (27 mg, 0.187 mmol)were added followed by addition of THF (0.5 mL) and methanol (0.5 mL).The mixture was heated for 15 hours and the solvents were removed invacuo. The resulting solid was purified by flash chromatography (20%ethyl acetate in hexanes) to give 14 a white crystalline solid (31.7 mg,96%). The ee was determined to be 97% using HPLC analysis on a CHIRALCELOD column, λ=486 nm. Retention times in 4% isopropanol in hexanes were10.1 min (major) and 11.1 min. R_(t)=0.29 on silica gel (10% ethylacetate:hexanes); mp 86-87° (Et₂O); [α]²⁵ _(D)=−208° (c=10.1, CHCl₃);R_(t)=0.39 on silica (20% ethyl acetate:hexanes). IR (KBr, cm⁻¹) 3277(br), 2971 (m), 1466(m), 1285(m), 1114(s), 1048(m), 979(m), 775(s); ¹HNMR (400 MHz, acetone-d) δ 7.60-7.62 (1H, m), 7.30-7.21 (2H, m),7.13-7.11 (1H, m), 6.50 (1H, dd, J=9.9, 1.8 Hz), 6.04 (1H, dd, J=9.9,2.2 Hz), 4.85 (1H, dd, J=9.9, 6.2 Hz), 3.50 (3H, s), 2.89 (1H, d, J=12.8Hz); ¹³C NMR (400 MHz, acetone-d) δ 138.5, 133.2, 129.1, 128.4, 128.3,128.2, 126.8, 126.3, 83.1, 73.0, 57.1. HRMS calcd for C₁₁H₁₂O₂ (M⁺):176.0837. Found: 176.0835.

(1S,2S)-2-(Ethoxy)-1,2-dihydro-naphthalen-1-ol (16): To a flame driedround bottom flask, [Rh(COD)Cl]₂ (2.1 mg, 0.043 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.087 mmol) and 13 (500 mg, 3.47 mmol)were added followed by addition of ethanol (4 mL) and THF (4 mL). Themixture was heated to reflux for five hours and the solvent was removedin vacuo. The resulting solid was purified by flash chromatography (20%ethyl acetate in hexanes) to give 16 as a white crystalline solid (553mg, 84%). The ee was determined to be 97% using HPLC analysis on aCHIRALCEL OD column, λ=254 nm. Retention times in 1.5% isopropanol inhexanes were 13.6 min and 14.2 min (major). R_(f)=0.26 on silica gel(20% ethyl acetate:hexanes); mp 33° (Et₂O); [α]²⁵ _(D)=185.9° (c=9.6,CHCl₃); IR (KBr, cm⁻¹) 3601 (br), 3040 (m), 2977 (s), 1454 (s), 1396(m), 1185 (s), 1104 (s); ¹H NMR (400 MHz, CDCl₃) δ 7.59-7.57 (1H, m),7.27-7.20 (2H, m), 7.07-7.05 (1H, m), 6.43 (1H, dd, J=9.9, 2.2 Hz), 6.01(1H, dd, J=9.9, 2.2 Hz), 4.90 (1H, d, J=10.6 Hz), 4.18 (1H, ddd, J=10.6,2.2, 2.2 Hz), 3.79 (1H, AB, dq, J=9.4, 6.9 Hz),), 3.58 (1H, AB, dq,J=9.4, 6.9 Hz), 2.65 (1H, s), 1.27 (3H, t, J=6.9 Hz),; ¹³C NMR (400 MHz,CDCl₃) δ 135.9, 131.9, 128.0, 127.8, 127.8, 126.1, 124.9, 80.7, 72.5,64.6, 15.5. HRMS calcd for C₁₂H₁₄O₂ (M⁺): 190.0994. Found: 190.0993.

(1S,2S)-2-(Isopropoxy)-1,2-dihydro-naphthalen-1-ol (18): To a flamedried round bottom flask, [Rh(COD)Cl]₂ (3.5 mg, 0.007 mmol),(S)-(R)-PPF-P^(t)Bu₂ (7.5 mg, 0.014 mmol) and 13 (100 mg, 0.694 mmol)were added followed by addition of THF (1.5 mL) and isopropanol (1.5mL). The mixture was heated to 80° C. for two hours and the solvent wasremoved in vacuo. The resulting oil was purified by flash chromatography(10% ethyl acetate in hexanes) to give 18 as a colourless oil (133.7 mg,94%). The ee was determined to be 92% using HPLC analysis on a CHIRALCELOD column, λ=486 nm. Retention times in 1.5% isopropanol in hexanes were9.7 min (major) and 10.7 min. R_(f)=0.42 on silica gel (10% ethylacetate:hexanes); [α]²⁵ _(D)=+154.0° (c=12.6, CHCl₃); IR (KBr, cm⁻¹)3435(br), 3038(w), 2952(s), 1454(m), 1249(s), 1087(s); ¹H NMR (400 MHz,CDCl₃) δ 7.61-7.58 (1H, m), 7.27-7.19 (2H, m), 7.06-7.04 (1H, m), 6.40(1H, dd, J=9.9, 2.0 Hz), 5.95 (1H, dd, J=9.9, 2.2 Hz), 4.87 (1H, d,J=10.8 Hz), 4.24 (1H, ddd, J=10.8, 2.2, 2.2 Hz), 3.85 (1H, h, J=6.2 Hz),2.98 (1H, s), 1.25 (6H, dd, J=8.8, 6.2 Hz); ¹³C NMR (400 MHz, CDCl₃)δ136.2, 132.3, 129.6, 128.0, 127.9, 127.8, 126.3, 125.0, 78.9, 73.0,71.1, 23.5, 22.4. HRMS calcd for C₁₃H₁₆O₂ (M⁺): 204.1150. Found:204.1150.

(1S,2S)-3-(1-propenyloxy)-1,2-dihydro-naphthalen-1-ol (19): To a flamedried round bottom flask, [Rh(COD)Cl]₂ (9.1 mg, 0.018 mmol),(S)-(R)-PPF-P^(t)Bu₂ (15 mg, 0.028 mmol) and 13 (1.06 g, 7.35 mmol) wereadded followed by addition of THF (1.5 mL) and allyl alcohol (2 mL, 29.4mmol). The mixture was heated to 80° C. for two hours and the THF wasremoved in vacuo. The resulting oil was purified by flash chromatography(10% ethyl acetate in hexanes) to give 19 as a colourless oil (898 mg,60%) which solidified on sitting. The ee was determined to be >99% usingHPLC analysis on a CHIRALCEL OD column, λ=486 nm. Retention times in1.5% isopropanol in hexanes were 15.2 min and 16.3 min (major).R_(f)=0.17 on silica gel (10% ethyl acetate:hexanes); mp 25-260 (Et₂O);[α]²⁵ _(D)=+195.1° (c=11.5, CHCl₃); IR (KBr, cm⁻¹) 3435(br), 3037(m),2857(s), 1454(s), 1165(s), 1083(s); ¹H NMR (400 MHz, CDCl₃) δ 7.61-7.58(1H, m), 7.27-7.20 (2H, m), 7.08-7.05 (1H, m), 6.44 (1H, dd, J=9.9, 2.0Hz), 6.00 (1H, dd, J=9.9, 2.4 Hz), 6.00-5.92 (1H, m), 5.32 (1H, ddd,J=17.2, 3.3, 1.6 Hz), 5.21 (1H, ddd, J=10.4, 2.9, 1.3 Hz), 4.94 (1H, d,J=10.2 Hz), 4.27 (1H, ddd, J=10.3, 2.2, 2.2 Hz),), 4.23 (1H, dddd,J=12.8, 5.5, 1.5, 1.5 Hz), 4.12 (1H, dddd, J=12.8, 5.9, 1.5, 1.5 Hz),3.09 (1H, s); ¹³C NMR (400 MHz, CDCl₃) δ135.8, 134.5, 131.8, 128.1,127.7, 127.6, 127.4, 126.1, 125.0, 117.5, 80.1, 76.7, 72.4, 70.2. HRMScalcd for C₁₄H[₄O₂ (M⁺):202.0994. Found: 202.0994.

(1S,2S)-2-(2-Trimethylsilyl-ethoxy)-1,2-dihydro-naphthalen-1-ol (20): Toa flame dried round bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.0087 mmol),(S)-(R)-PPF-P^(t)Bu₂ (9.4 mg, 0.0174 mmol) and 13 (100 mg, 0.694 mmol)were added followed by addition of THF (1.25 mL) andtrimethylsilylethanol (1.25 mL). The mixture was heated to reflux fortwo hours and the THF was removed in vacuo. The resulting oil waspurified by flash chromatography (10% ethyl acetate in hexanes) to give20 as a colourless oil (84.7 mg, 53%). The ee was determined to be 95%using HPLC analysis on a CHIRALCEL OD column, λ=486 nm. Retention timesin 0.5% isopropanol in hexanes were 17.9 min and 18.5 min (major).R_(f)=0.25 on silica gel (10% ethyl acetate:hexanes); [α]²⁵ _(D)=+119.2°(c=13.0, CHCl₃); IR (KBr, cm⁻¹) 3447(br), 3037(m), 2972(s), 1454(m),1381(m), 1118(s), 1078(s); ¹H NMR (400 MHz, CDCl₃) δ 7.59-7.57 (1H, m),7.28-7.21 (2H, m), 7.08-7.06 (1H, m), 6.43 (1H, dd, J=9.9, 2.0 Hz), 6.03(1H, dd, J=9.9, 2.2 Hz), 4.89 (1H, d, J=10.6 Hz), 4.18 (1H, ddd, J=10.6,2.2, 2.2 Hz), 3.85-3.78 (2H, m), 3.63-3.56 (2H, m), 2.79 (1H, s),1.05-0.97 (2H, m), 0.36 (9H, m); ¹³C NMR (400 MHz, CDCl₃) δ. 135.9,132.0, 127.9, 127.9, 127.8, 127.6, 126.1, 124.9, 80.4, 72.6, 66.5, 18.6,−1.4. HRMS calcd for C₁₅H₂₂O₂Si (M⁺): 262.1389. Found: 262.1388.

(1S,2S)-2-Benzyloxy-1,2-dihydro-naphthalen-1-ol (21): To a flame driedround bottom flask, [Rh(COD)Cl]₂ (9.0 mg, 0.018 mmol),(S),(R)-PPF-P^(t)Bu₂ (19.0 mg, 0.035 mmol), and 13 (1.00 g, 6.94 mmol)were added followed by addition of THF (1.8 mL) and benzylalcohol (3.6mL, 34.7 mmol) and heating to 80° C. for 24 hours. The THF was thenremoved in vacuo and the resulting oil was purified by flashchromatography (10% ethyl acetate in hexanes) to give 21 as acrystalline solid (1.22 g, 70%). The ee was determined to be >98% usingHPLC analysis on a CHIRALCEL OD column, λ=486 rim. Retention times in1.5% isopropanol in hexanes were 29.0 min and 32.5 min (major).R_(f)=0.34 on silica gel (20% ethyl acetate:hexanes); mp 52-54° (Et₂O);[α]²⁵ _(D)=+167.3° (c=10.0, CHCl₃); IR (KBr, cm⁻¹) 3305 (br), 3020 (w),2876 (w), 1496 (m), 1352 (m), 1281 (m), 1169 (m), 1050 (s), 777 (s); ¹HNMR (400 MHz, CDCl₃) δ 7.58-7.56 (1H, m), 7.41-7.22 (7H, m), 7.22-7.07(1H, m), 6.46 (1H, dd, J=9.9, 2.1 Hz), 6.05 (1H, dd, J=9.9, 2.1 Hz),4.98 (1H, d, J=10.4 Hz), 4.78 (1H, d, J=11.7 Hz), 4.63 (1H, d, J=11.7Hz), 4.33 (1H, ddd, J=10.4, 2.2, 2.2 Hz), 2.61 (1H, s); ¹³C NMR (400MHz, CDCl₃) δ 138.0, 135.9, 131.9, 128.5, 128.3, 128.1, 127.9, 127.9,127.8, 127.4, 126.2, 125.1, 80.4, 72.6, 71.3. HRMS calcd for C₁₇H₁₆O₂(M⁺): 252.1150. Found: 252.1148.

(1S,2S)-2-(4-Methoxybenzyloxy-1,2-dihydro-naphthalen-1-ol (22): To aflame dried round bottom flask, [Rh(COD)Cl]₂ (6.0 mg, 0.012 mmol),(S),(R)-PPF-P^(t)Bu₂ (13.0 mg, 0.024 mmol), and 13 (693 mg, 4.81 mmol)were added followed by addition of THF (1.5 mL) and anisyl alcohol (3.0mL, 24.1 mmol) and heating to 80° C. for 24 hours. The THF was thenremoved in vacuo and the resulting oil was purified by flashchromatography (20% ethyl acetate in hexanes) to give 22 as acrystalline solid (1.18 g, 87%). The ee was determined to be 97% usingHPLC analysis on a CHIRALCEL OD column, λ=486 mm. Retention times in1.5% isopropanol in hexanes were 37.1 min and 42.1 min (major).R_(f)=0.53 on silica gel (30% ethyl acetate:hexanes); mp 63-64° (Et₂O);[α]²⁵ _(D)=+138.5° (c=10.5, CHCl₃); IR (KBr, cm⁻¹) 3435(br), 3035(m),2836(s), 1612(s), 1513(s), 1454(m), 1249(s), 1082(s); ¹H NMR (400 MHz,CDCl₃) δ 7.59-7.57 (1H, m), 7.32 (2H, ddd, J=8.7, 2.8, 1.9 Hz),7.28-7.22 (1H, m), ), 6.90 (2H, ddd, J=8.7, 2.8, 1.9 Hz), 6.46 (1H, dd,J=9.9, 2.1 Hz), 6.04 (1H, dd, J=9.9, 2.4 Hz), 4.96 (1H, d, J=10.1 Hz),4.64 (1H, dd, J=57.1, 11.4 Hz), 4.32 (1H, ddd, J=10.2, 2.2, 2.2 Hz),3.80 (1H, s), 2.96 (1H, s); ¹³CNMR (400 MHz, CDCl₃) δ 159.2, 135.9,131.9, 129.9, 129.5, 128.1, 127.8, 127.6, 127.5, 126.1, 125.0, 113.8,80.0, 72.5, 70.9, 55.1. HRMS calcd for C₁₇H₁₆O₂ (M⁺): 252.1150. Found:252.1148.

(1S,2S)-2-(2,2,2-Trifluoro-ethoxy)-1,2-dihydro-naphthalen-1-ol (17): Toa flame dried round bottom flask, [Rh(COD)Cl]₂ (2.1 mg, 0.043 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.087 mmol) and 13 (500 mg, 3.47 mmol)were added followed by addition of trifluoroethanol (4 mL) and THF (4mL). The mixture was heated to reflux for three hours and the solventwas removed in vacuo. The resulting solid was purified by flashchromatography (10% ethyl acetate in hexanes) to give 17 as a whitecrystalline solid (594 mg, 70%). The ee was determined to be 98% usingHPLC analysis on a CHIRALCEL OD column, λ=254 nm. Retention times in 4%isopropanol in hexanes were 11.3 min (major) and 13.3 min. R_(f)=0.41 onsilica gel (20% ethyl acetate:hexanes); mp 79-80° (Et₂O); [α]²⁵_(D)=145.4° (c=12.6, CHCl₃); IR (KBr, cm⁻¹) 3354 (br), 3036 (w), 2939(w), 1455 (w), 1275 (s), 1169 (s), 1050(m), 977 (m); ¹H NMR (400 MHz,CDCl₃) δ 7.57-7.55 (1H, m), 7.30-7.23 (2H, m), 7.10-7.08 (1H, m), 6.48(1H, dd, J=9.9, 2.0 Hz), 5.94 (1H, dd, J=9.9, 2.4 Hz), 4.96 (1 H, d,J=2.2 Hz), 4.38 (1H, ddd, J=9.9, 2.4, 2.2 Hz), 4.03 (2H, q, J^(H−F)=8.6Hz), 2.55 (1H, s); ¹³C NMR (400 MHz, CDCl₃) δ 135.5, 131.7, 129.2,128.3, 128.1, 126.6, 125.9, 125.2, 122.4, 83.0, 72.8, 67.0 (q,J^(C−F)=34.4 Hz). HRMS calcd for C₁₂H₁₁O₂F₃ (M⁺): 244.0711. Found:244.0720.

(1S,2S)-2-(2,2,2-Trifluoro-1-trifluoromethyl-ethoxy)-1,2-dihydro-naphthalen-1-ol(23): To a flame dried round bottom flask, [Rh(COD)Cl]₂ (1.7 mg, 0.003mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.007 mmol) and 13 (55 mg, 0.382mmol) were added followed by addition of THF (2.0 mL) andhexafluoroisopropanol (240 mg, 1.74 mmol). The mixture was heated toreflux for two hours and the solvent was removed in vacuo. The resultingsolid was purified by flash chromatography (10% ethyl acetate inhexanes) to give 23 as a white solid (107.1 mg, 90%). The ee wasdetermined to be 93% using HPLC analysis on a CHIRALCEL OD column, λ=486nm. Retention times in 1.5% isopropanol in hexanes were 11.3 min and17.6 min (major); R_(f)=0.28 on silica gel (10% ethyl acetate:hexanes);mp 88.5-90° (Et₂O); [α]²⁵ _(D)=+101.8° (c=10.9, CHCl₃); IR (KBr, cm⁻¹)3191 (br), 2937 (m), 1379 (s), 1280 (s), 1247 (s), 1194 (s), 1100 (s),954 (s), 753 (m); ¹H NMR (400 MHz, CDCl₃) δ 7.55-7.53 (1H, m), 7.31-7.26(2H, m), 7.11-7.09 (1H, m), 6.49 (1H, dd, J=9.9, 2.1 Hz), 5.92 (1H, dd,J=9.9, 2.4 Hz), 5.07 (1H, dd, J=9.7, 5.0 Hz), 4.63 (1H, ddd, J=9.9, 1.5,1.5 Hz), 4.58 (1H, h, J^(H−F)=6.1 Hz), 2.50 (1H, d, J=4.2 Hz); ¹³C NMR(400 MHz, CDCl₃) δ 135.2, 131.5, 129.7, 128.5, 128.3, 126.7, 125.2,122.9, 120.1, 85.4, 75.4 (h, J^(C−F)=32.2 Hz), 73.5. HRMS calcd forC₁₃H₁₀O₂F₆ (M⁺): 312.0585 Found: 312.0574.

6,7-Difluoro-1,4-epoxy-1,4-dihydronaphthalene (24). To3,4-difluoro-1,2-dibromo-benzene (0.75 g, 2.78 mmol) and furan (1 mL,14.7 mmol) in Et₂O (15 mL) at −78° C. was added BuLi (1.1 mL, 2.5M inhexanes, 2.75 mmol) dropwise. The reaction was stirred for two hours at−78° C. and then was allowed to warm to room temperature. After 2 hours,the reaction mixture was quenched with water dropwise and then waspoured into water. The organic layer was separated and the aqueous layerwas extracted three times with Et₂O. The combined organic layers werewashed with brine, dried over MgSO₄, concentrated and chromatographed(25% ethyl acetate:hexanes) on silica gel to give 24 (350 mg, 70%) as acolourless oil. R_(f)=0.21 on silica gel (20% ethyl acetate:hexanes); bp40° C. @ 0.5 mmHg]; IR (neat, cm⁻¹), 3017 (M), 1624 (s), 1465 (s), 1365(s), 1253 (s), 1190 (m), 1040 (s), 857 (s). ¹H NMR (400 MHz, CDCl₃) δ7.06 (2H, dd, J^(H−F)=7.7, 7.7 Hz), 7.01 (2H, s), 5.67 (2H, s); ¹³C NMR(400 MHz, CDCl₃) δ 147.2 (dd, J^(C−F)=247.9, 14.5 Hz), 145.1 (dd,J^(C−F)=4.3, 4.3 Hz), 143.1, 110.8 (m), 82.1. HRMS calcd for C₁₀H₆O(M⁺): 180.0387. Found: 180.0394.

5,8-epoxy-5,8-dihydronaphtho[2,3-d][1,3]dioxole (25): To3,4-dibromobenzo-1,3-dioxolane (1.54 g, 5.50 mmol) and furan (4 g, 58.8mmol) in PhMe (55 mL) at −78° C. was added BuLi (2.2 mL, 2.5M inhexanes, 5.5 mmol) dropwise. The reaction was stirred for two hours at−78° C. and the allowed to warm to rt. After 3 hours, MeOH (2 mL) wasadded and the reaction mixture was poured into water. The organic layerwas separated and the aqueous layer was extracted three times with Et₂O.The combined organic layers were washed with brine, dried over MgSO₄,and concentrated. Recrystallization from hexanes gave 25 (560 mg, 54%)as white crystals). R_(f)=0.47 on silica gel (30% ethylacetate:hexanes); mp 111-112° C. (Et₂O); IR (KBr, cm⁻¹) 2895, 1455,1292, 1138, 1038, 1014, 848; ¹H NMR (400 MHz, CDCl₃) δ 7.02 (2H, dd,J=0.9, 0.9 Hz), 6.82 (2H, s), 5.92 (1H, d, J=1.5 Hz), 5.87 (1H, d, J=1.5Hz), 5.62 (2H, s); ¹³C NMR (400 MHz, CDCl₃) δ 144.3, 143.3, 103.9,101.1, 82.4. HRMS calcd for C₁₁H₈O₂ (M⁺): 188.0473. Found: 188.0463.

5,6-Dibromo-4,7-dimethyl-1,4-epoxy-1,4-dihydronaphthalene (26): Totetrabromo para-xylene (2.1 g, 5.0 mmol) and furan (4 g, 58.8 mmol) inPhMe (55 mL) at −78° C. was added BuLi (2.2 mL, 2.5M in hexanes, 5.5mmol) dropwise. The reaction was stirred for two hours at −78° C. andthe allowed to warm to rt. After 3 hours, MeOH (2 mL) was added and thereaction mixture was poured into water. The organic layer was separatedand the aqueous layer was extracted three times with Et₂O. The combinedorganic layers were washed with brine, dried over MgSO₄, andconcentrated. Flash chromatography on silca gel gave 26 (185 mg, 50%) asa white solid. The spectral data correlates well with the literaturevalues.²²

(1S,2S)-6,7-Difluoro-2-methoxy-1,2-dihydro-naphthalen-1-ol (27): To aflame dried round bottom flask, [Rh(COD)Cl]₂ (2.5 mg, 0.005 mmol),(S)-(R)-PPF-P^(t)Bu₂ (5.4 mg, 0.010 mmol) and 24 (72 mg, 0.40 mmol) wereadded followed by addition of THF (1.0 mL) and methanol (1.0 mL). Themixture was heated to reflux for 1 hour. The solvents were then removedin vacuo. The resulting solid was purified by flash chromatography (20%ethyl acetate in hexanes) to give 27 as a white crystalline solid (74.9mg, 88%). The ee was determined to be 96.4% using HPLC analysis on aCHIRALCEL OD column, λ=486 nm. Retention times in 4% isopropanol inhexanes were 8.9 min and 10.1 min (major). R_(f)=0.27 on silica gel (30%ethyl acetate:hexanes); mp 129-131° (Et₂O); [α]²⁵ _(D)=+134.4° (c=9.3,CHCl₃); IR (KBr, cm⁻¹) 3269 (br), 2937 (w), 1597 (m),1503 (s), 1306 (s),1103 (s), 893 (s); ¹H NMR (400 MHz, CDCl₃) δ 7.40 (1H, ddd,J^(H−F)=10.8, 7.8 Hz, J^(H−H)=0.6 Hz), 6.85 (1H, dd, J^(H−F)=10.9, 7.8Hz), 6.31 (1H, dd, J=10.0, 2.0 Hz), 6.05 (1H, dd. J=10.0, 2.0 Hz), 4.79(1H, d, J=1.0 Hz), 4.05 (1H, ddd, J=11.0, 2.0, 2.0 Hz), 3.49 (3H, s),2.94 (1H, d, J=2.2 Hz); ¹³C NMR (400 MHz, CDCl₃) δ 151.0 (d,J^(H−F)=12.5 Hz), 148.5 (dd, J^(H−F)=12.5, 2.9 Hz), 133.2 (dd,J^(H−F)=5.2, 3.6 Hz), 128.9 (dd, J^(H−F)=6.6, 4.4 Hz), 128.0 (d,J^(H−F)=2.2 Hz), 126.5 (dd, J^(H−F)=2.2, 1.5 Hz), 115.1 (d, J^(H−F)=18.3Hz), 114.8 (d, J^(H−F)=19.8 Hz), 82.3, 72.0, 57.0. HRMS calcd for ClH₁₀O₂F₂ (M⁺): 212.0649. Found: 212.0658.

(1S,2S)-6-Methoxy-5,6-dihydro-naphtho[2,3-d][1,3]dioxol-5-ol (28): To aflame dried round bottom flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0069 mmol) and 25 (100 mg, 0.694 mmol)were added followed by addition of THF (1.0 mL) and methanol (1.0 mL)and heating to reflux for 30 minutes. The solvents were then removed invacuo. The resulting solid was purified by flash chromatography (30%ethyl acetate in hexanes) to give 28 as a white crystalline solid (127.5mg, 90%). The ee was determined to be 95% using HPLC analysis on aCHIRALCEL OD column, λ=486 nm. Retention times in 4% isopropanol inhexanes were 19.2 min (major) and 22.6 min. R_(f)=0.24 on silica (30%ethyl acetate:hexanes); mp 117-119° (Et₂O); [α]²⁵ _(D)=+298.70 (c=11.1,CHCl₃); IR (KBr, cm⁻¹) 3248 (br),2926 (s), 1600 (m), 1483 (s), 1260 (s),1113 (s), 941 (s), 876 (s); ¹H NMR (400 MHz, acetone-d) δ 7.06 (1H, s),6.65 (1H, s), 6.35 (1H, dd, J=10.0, 2.0 Hz), 5.94 (2H, dd, J=9.8, 1.0Hz), 5.91 (1H, dd, J=10.0, 2.5 Hz), 4.72 (1H, dt, J=9.9 Hz), 4.02 (1H,dt, J=10.3, 2.2 Hz), 3.48 (3H, s), 2.87 (1H, d, J=13.2 Hz); ¹³C NMR (400MHz. acetone-d) δ 147.8, 147.6, 133.0, 128.1, 127.2, 127.2, 107.5,107.5, 101.9, 82.1, 73.0, 57.0. HRMS calcd for C₁₂H₁₂O₄ (M⁺): 220.0736.Found: 220.0684.

(1S,2S)-6,7-Dibromo-2-methoxy-5,8-dimethyl-1,2-dihydro-naphthalen-1-ol(29): To a flame dried round bottom flask, [Rh(COD)Cl]₂ (1.5 mg, 0.0029mmol), (R)-(S)-PPF-P^(t)Bu₂ (3.2 mg, 0.0059 mmol) and 26 (195 mg, 0.59mmol) were added followed by addition of trifluoroethanol (1.0 mL) andmethanol (1.0 mL). The mixture was heated to reflux for 20 hours. Thesolvents were then removed in vacuo. The resulting solid was purified byflash chromatography (50% ethyl acetate in hexanes) to give 29 as awhite crystalline solid (171.6 mg, 79%). The ee was determined to be 97%using HPLC analysis on a CHIRALCEL OD column, λ=486 nm. Retention timesin 4% isopropanol in hexanes were 16.8 min (major) and 19.3 min.R_(f)=0.39 on silica gel (50% ethyl acetate:hexanes); mp 114-116°(Et₂O); [α]²⁵ _(D)=−197.1° (c=10.0, CHCl₃); IR (KBr, cm⁻¹) 3349(s), 2901(m), 1700(w), 1532 (w), 1404(m), 1258 (m), 1081 (s), 936 (s); ¹H NMR(400 MHz, CDCl₃) δ 6.96-6.93 (1H, m), 6.23-6.19 (1H, m), 4.89 (1H, s),3.96-3.90 (1H, m), 3.38-3.35 (3H, m), 2.61-2.57 (3H, m), 2.54 (3H, s),1.82-1.54 (1H, m); ¹³C NMR (400 MHz, CDCl₃) δ 137.3, 134.4, 133.2,129.7, 129.5, 129.0, 128.1, 125.3, 75.3, 66.6, 56.6, 21.0, 20.6. HRMScalcd for C₁₃H₁₆O₂Br₂ (M⁺): 361.9518. Found: 361.9335.

Example 4 Compounds Formed From Reactions Involving CarboxylateNucleophiles

(1R*,2R*)-Acetic acid 1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester (2):To a flame dried round bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.008 mmolDPPF (9.6 mg, 0.017 mmol), 1 (50 mg, 1.39 mmol), and sodium acetate (142mg, 1.74 mmol) were added followed by addition of THF (2 mL) andtriethylamine hydrochloride (239 mg, 1.74 mmol). The mixture was heatedat reflux for 3 hours and the solvents were removed in vacuo. Theresulting mixture was purified by flash chromatography (30% ethylacetate in hexanes) to give 2 as a crystalline solid (41 mg), 63%).R_(f)=0.26 on silica gel (20% ethyl acetate:hexanes); mp 67-68° (Et₂O);IR (KBr, cm⁻¹) ¹H NMR (400 MHz, CDCl₃) δ 7.54-7.53 (1H, m), 7.29-7.24(2H, m), 7.10-7.08 (1H, m), 6.50 (1H, dd, J=3.9, 1.3 Hz), 5.85 (1H, dd,J=9.9, 3.1 Hz), 5.59 (1H, ddd, J=9.0, 2.8, 1.9 Hz), 4.92 (1H, d, J=9.0Hz), 2.64 (1H, s), 2.12 (3H, s); ¹³C NMR (400 MHz, CDCl₃) δ 171.3,135.2, 131.5, 129.5, 128.3, 126.7, 126.0, 125.4, 75.3, 71.7, 21.2. HRMScalcd for C₁₂H₁₂O₃ (M): 204.0786. Found: 204.0791.

(1R*,2R*)-Propionic acid 1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester(3): To a flame dried round bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.0087mmol), DPPF (9.6 mg, 0.017 mmol) and 1 (50 mg, 0.347 mmol) were addedfollowed by addition of THF (2.5 mL), triethylamine (242 μL, 1.735 mmol)and propionic acid (130 μL, 1.735 mmol). The mixture was heated atreflux for 3 hours and the solvents were removed in vacuo. The resultingmixture was purified by flash chromatography (20% ethyl acetate inhexanes) to give 3 a white crystalline solid (50 mg, 66%). R_(f)=0.24 onsilica gel (% 20 ethyl acetate:hexanes); mp 55-56° (Et₂O); IR (KBr,cm⁻¹) 3491 (br), 3048 (w), 2984 (w), 1739 (s), 1454 (m), 1363 (w), 1182(s), 1083 (m). ¹H NMR (400 MHz, CDCl₃) δ 7.55-7.52 (1H, m), 7.29-7.24(2H, m), 7.11-7.08 (1H, m), 6.50 (1H, dd, J=10.0, 2.0 Hz), 5.85 (1H, dd,J=12.8, 2.8 Hz), 5.61 (1H, ddd, J=9.2, 2.8, 2.0 Hz), 4.93 (1H, d, J=9.2Hz), 2.40 (2H, qd, J=7.6, 1.2 Hz), 1.16 (3H, t, J=7.6 Hz); ¹³C NMR (400MHz, CDCl₃) δ 174.8, 135.3, 131.5, 129.4, 128.3, 128.3, 126.7, 125.9,125.5, 75.2, 71.9, 27.7, 9.0. HRMS calcd C₁₃H₁₄O₃ (M⁺): 218.0943. Found:218.0938

(1R,2R)-Benzoic acid 1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester (4): Toa flame dried round bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.0087 mmol),(R)—(S)-BPPFA (9.6 mg, 0.017 mmol) and 1 (100 mg, 0.694 mmol) were addedfollowed by addition of THF (4 mL), triethylamine (483 μL, 3.47 mmol)and benzoic acid (424 mg, 3.47 mmol). The mixture was heated at refluxfor 6 hours and the solvents were removed in vacuo. The resultingmixture was purified by flash chromatography (20% ethyl acetate inhexanes) to give 4 a white crystalline solid (129 mg, 70%). The ee wasdetermined to be 76% using HPLC analysis on a CHIRALCEL OD column, 10%isopropanol in hexanes, λ=254 nm. Retention times were 10.0 min (major)and 12.9 min. R_(f)=0.3 on silica gel (10% ethyl acetate:hexanes); mp107-109° (Et₂O); [α]²⁵ _(D)=−298.4° (c=11.3, CHCl₃); IR (KBr, cm⁻¹) 3619(br), 3071 (w), 2977 (w), 1724 (s), 1451 (m), 1324 (m), 1265 (s), 1110(s). ¹H NMR (400 MHz, CDCl₃) δ 8.10 (2H, d, J=7.6 Hz), 7.64-7.59 (2H,m), 7.48-7.45 (2H, m), 7.34-7.32 (2H, m), 7.13-7.11 (1H, m), 6.55 (1H,d, J=10.0 Hz), 5.97 (1H, dd, J=9.8, 2.9 Hz), 5.86 (1H, ddd, J=9.8, 2.0,2.0 Hz), 5.11 (1H, d, J=9.0 Hz), 2.84 (1H, s); ¹³C NMR(400 MHz, CDCl₃) δ166.9, 135.3, 133.3, 131.6, 129.9, 129.8, 129.7, 128.4, 128.4, 128.4,126.8, 126.1, 125.5, 76.1, 71.9. HRMS calcd for C₁₇H₁₄O₃ (M⁺): 266.0943.Found: 266.0938.

(1R*,2R*)-Formic acid 1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester (5):To a flame dried round bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.0087 mmol),DPPF (9.6 mg, 0.017 mmol), 1 (100 mg, 0.694 mmol), and ammonium formate(219 mg, 3.47 mmol), were added followed by addition of THF (5 mL). Themixture was heated at reflux for 3 hours and the solvents were removedin vacuo. The resulting mixture was purified by flash chromatography(30% ethyl acetate in hexanes) to give 5 a white crystalline solid (84mg, 64%). R_(f)=0.25 on silica gel (30% ethyl acetate:hexanes); mp133-1350 (Et₂O); IR (KBr, cm⁻¹) 3146 (br), 2935 (w), 1720 (s), 1482 (w),1186 (s), 1049 (m), 968 (m); ¹H NMR (400 MHz, CDCl₃) δ 8.17 (1H, d,J=0.8 Hz), 7.52-7.50 (1H, m), 7.29-7.27 (2H, m), 7.13-7.11 (1H, m), 6.54(1H, dd, J=9.6, 1.6 Hz), 5.88 (1H, dd, J=9.6, 2.8 Hz), 5.71-5.68 (1H,m), 4.96 (1H, d, J=8.8 Hz), 2.8 (1H, s); ¹³C NMR (400 MHz, CDCl₃) δ160.9, 134.8, 131.4, 130.0, 128.5, 126.9, 126.1, 124.6, 74.8, 71.4. HRMScalcd for C₁₁H₁₀O₃ (M⁺): 190.0630. Found: 190.0625.

(1R*,2R*)-2-Methyl acrylic acid1-hydroxy-1,2-dihydro-naphthalen-2-yl-ester (6): To a flame dried roundbottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.0087 mmol), DPPF (9.6 mg, 0.017mmol) and 1 (50 mg, 0.347 mmol) were added followed by addition of THF(2.5 mL), triethylamine (242 μL, 1.735 mmol) and methacrylic acid (147μL, 1.735 mmol). The mixture was heated at reflux for 3 hours and thesolvents were removed in vacuo. The resulting mixture was purified byflash chromatography (30% ethyl acetate in hexanes) to give 6 a whitecrystalline solid (50 mg, 63%). R_(f)=0.32 on silica gel (20% ethylacetate:hexanes); mp 80-82° (Et₂O); IR (KBr, cm⁻¹) 3450 (br), 3030 (w),2928 (w), 1722 (s), 1637 (m), 1454 (m), 1289 (m), 1163 (s); ¹H NMR (400MHz, CDCl₃) δ 7.56-7.55 (1H, m), 7.29-7.24 (2H, m), 7.10-7.09 (1H, m),6.51 (1H, dd, J=9.9, 1.9 Hz), 6.15 (1H, s), 5.87 (1H, dd, J=9.9, 3.0Hz), 5.67 (1H, ddd, J=9.3, 2.1, 2.1 Hz), 5.61 (1H, s), 5.01 (1H, dd,J=9.0, 5.7 Hz), 2.74 (1H, d, J=6.1 Hz), 1.96 (3H, s); ¹³C NMR (400 MHz,CDCl₃) δ 167.6, 135.9, 135.3, 131.5, 129.4, 128.3, 128.2, 126.6, 126.4,125.8, 125.5, 75.9, 71.9, 18.3. HRMS calcd C₁₄H₁₂O₂ (M⁺-H₂O): 212.0837.Found: 212.0831

(1R*,2R*)-Malonic acid ethyl ester(1-hydroxy-1,2-dihydro-naphthalen-2-yl) ester (7): To a flame driedround bottom flask, [Rh(COD)Cl]₂ (8.6 mg, 0.017 mmol DPPF (19.2 mg,0.035 mmol), 1 (200 mg, 1.39 mmol), ethyl malonate potassium salt (590mg, 3.47 mmol), and triethylamine hydrochloride (478 mg, 3.47 mmol) wereadded followed by addition of THF (8 mL). The mixture was heated atreflux for 3 hours and the solvents were removed in vacuo. The resultingmixture was purified by flash chromatography (30% ethyl acetate inhexanes) to give 7 a colourless oil (300 mg), 79%). R_(f)=0.29 on silicagel (30% ethyl acetate:hexanes); IR (KBr, cm⁻¹) 3470 (br), 2983 (w),1731 (s), 1453 (w), 1370 (m), 1150 (s), 1031 (m); ¹H NMR (400 MHz,CDCl₃) δ 7.56-7.54 (1H, m), 7.27-7.21 (2H, m), 7.08-7.06 (1H, m), 6.48(1H, dd, J=9.9, 2.1 Hz), 5.83 (1H, dd, J=9.7, 2.8 Hz), 5.70 (1H, ddd,J=9.7, 2.5, 2.2 Hz), 4.97 (1H, d, J=9.5 Hz), 4.18 (2H, q, J=7.2 Hz),3.43 (2H, dd, J=23.6, 15.9 Hz), 3.21 (1H, s), 1.25 (3H, t, J=7.1 Hz);¹³C NMR (400 MHz, CDCl₃) δ 167.1, 166.5, 135.0, 131.5, 129.6, 128.3,128.1, 126.6, 125.6, 125.1, 77.0, 71.6, 61.9, 41.6, 14.0. HRMS calcd forC₁₅H₁₄O₄ (M³⁰ -H₂O): 258.0892. Found: 258.0899.

(1R*,2R*)-Malonic acid(1-tert-butyldimethylsiloxy-1,2-dihydro-naphthalen-2-yl) ester ethylester (8): To a dried round bottom flask, 7 (270 mg, 0.98 mmol),imidazole (134 mg, 1.96 mmol), dimethylaminopyridine (6 mg, 0.05 mmol)were dissolved in dichloromethane (4 mL). Tert-butyldimethylsilylchloride (222 mg, 1.47 mmol) was then added portionwise and allowed toreact for 24 hours. The reaction was then quenched with water, extractedwith dichloromethane, dried over Na₂SO₄ and concentrated in vacuo. Flashchromatography (10% ethyl acetate in hexanes) gave a colourless oil 8(343 mg, 90%). R_(f)=0.48 on silica gel (10% ethyl acetate:hexanes.IR(KBr, cm⁻¹) 2983 (w), 1731 (s), 1453 (w), 1370(m), 1150(s), 1031 (m);¹H NMR (400 MHz, CDCl₃) δ 7.41-7.39 (1H, m), 7.24-7.22 (2H, m),7.07-7.05 (1H, m), 6.47 (1H, dd, J=9.9, 1.8 Hz), 5.83 (1H, dd, J=9.7,2.7 Hz), 5.60 (1H, ddd, J=9.3, 2.9, 2.0 Hz), 5.00 (1H, dd, J=9.3, 0.5Hz), 4.22-4.15 (2H, m), 3.40 (2H, dd, J=19.6, 16.0 Hz), 1.57 (1H, s),1.25 (3H, t, J=7.1 Hz), 0.92 (9H, s), 0.13 (3H, s), 0.09 (3H, s); ¹³CNMR (400 MHz, CDCl₃) δ 166.3, 166.2, 136.2, 132.1, 129.4, 128.0, 127.9,126.5, 125.9, 125.7, 76.4, 71.6, 61.6, 41.7, 25.8, 18.1, 14.0, −4.3,−4.5. HRMS calcd for C₁₇H₂₁O₅Si (M⁺-C₄H₉): 333.1158. Found: 333.1149.

(1S*,2S*)-(4-Tert-butyldimethylsiloxy-1,4-dihydro-naphthalen-2-yl)acetic acid ethyl ester (9): To a dried round bottom flask, 8 (100 mg,0.256 mmol) was dissolved in THF (4 mL). Potassium hydride (11.3 mg,0.28 mmol) was then added portionwise and allowed to react for fiveminutes at room temperature. Triphenylphosphine (34.1 mg, 0.13 mmol) wasthen added followed by Pd(PPh₃)₄ (14.8 mg, 0.013 mmol). The reaction wasthen heated to reflux for two hours. The solvent was then removed invacuo and the resulting oil purified by flash chromatography (5% ethylacetate in hexanes) giving 9 a colourless oil (54 mg, 61%). R_(f)=0.27on silica gel (5% ethyl acetate:hexanes); IR (KBr, cm⁻¹) 3036(w),2956(s), 1735(s), 1472 (m), 1257(s), 1077(s); ¹H NMR (400 MHz, CDCl₃) δ7.54-7.52 (1H, m), 7.30-7.23 (3H, m), 6.09 (1H, ddd, J=2.4, 4.6, 10.2Hz), 6.02 (1H, ddd, J=10.2, 2.0, 0.5 Hz), 5.22-5.21 (1H, m), 4.15 (2H,q, J=7.2 Hz), 3.92-3.87 (1H, m), 2.62 (1H, dd, J=15.7, 5.7 Hz), 2.39(1H, dd, J=15.2, 9.0 Hz), 1.25 (3H, t, J=7.2 Hz), 0.98 (9H, s), 0.21(3H, s), 0.15 (3H, s); ¹³C NMR (400 MHz, CDCl₃) δ 171.7, 138.3, 136.1,131.8, 128.2, 127.2, 127.0, 126.9, 126.6, 65.3, 60.5, 42.7, 36.5, 25.9,18.2, 14.2, −4.2, −4.5. HRMS calcd C₁₇H₂₁O₅Si (M⁺-C₄H₉): 289.1260.Found: 289.1257

Example 5 Compounds Formed in Reactions Involving Nitrogen Nucleophiles

(1R,2R)-2-(1-hydroxy-1,2-dihydro-naphthalen-2-yl)-isoindole-1,3-dione(2): To a flame dried round bottom flask, [Rh(COD)Cl]₂ (5.4 mg, 0.011mmol), (R)-(S)-BPPFA (12.2 mg, 0.022 mmol), phthalimide (510 mg, 3.47mmol) and 1 (100 mg, 0.69 mmol) were added. THF (4 mL) was then added,followed by heating to 80° C. for 3 days. The reaction mixture was thenpoured in to water and extracted three times with ethyl acetate. Theorganic layers were combined, washed with brine dried over Na₂SO₄, andconcentrated in vacuo. The resulting solid was purified by flashchromatography (30% ethyl acetate in hexanes) to give 2 as a whitecrystalline solid (103.5 mg, 52%). The ee was determined to be 74% usingHPLC analysis on a CHIRALCEL OD column, λ=486 nm. Retention times in 10%isopropanol in hexanes were 21.1 min (major) and 29.1 min. R_(f)=0.36 onsilica gel (30% ethyl acetate:hexanes); mp 175-176° (dec); [α]²⁵_(D)=−6.1° (c=12.9, CHCl₃); IR (KBr, cm⁻¹) 3536 (br), 3067 (w), 2921(w), 1772 (m), 1693 (s), 1388 (s), 1084 (m), 955 (m), 719 (s); ¹H NMR(400 MHz, CDCl₃) δ 7.78-7.75 (2H, m), 7.68-7.64 (2H, m), 7.57-7.55 (1H,m), 7.26-7.22 (2H, m), 7.09-7.07 (1H, m), 6.51 (1H, dd, J=9.7, 2.7 Hz),5.84 (1H, ddd, J=9.7.2.7, 2.2 Hz), 5.48 (1H, d, J=12.8 Hz), 5.12 (1H,ddd, J=12.8, 2.5, 2.4 Hz), 2.82 (1H, s); ¹³C NMR (400 MHz, CDCl₃) δ168.6, 137.3, 134.2, 132.6, 132.1, 128.7, 128.2, 128.1, 126.9, 126.5,124.4, 123.5, 70.9, 55.3. HRMS calcd for C₁₈H₁₁NO₂ (M⁻-H₂O): 273.2939.Found: 273.0793.

(1S,2S)-N-(1-Hydroxy-1,2-dihydro-naphthalen-2-yl)-benzene sulfonamide(3): To a flame dried round bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.0087mmol), (S)-(R)-PPF-P^(t)Bu₂ (9.4 mg, 0.0173 mmol), benzenesulfonamide(545 mg, 3.47 mmol) and 1 (100 mg, 0.69 mmol) were added. THF (2 mL) wasthen added, followed by heating to 80° C. for 12 hours. The reactionmixture was then poured into water and extracted three times with ethylacetate. The organic layers were combined, washed with brine dried overNa₂SO₄, and concentrated in vacuo. The resulting solid was purified byflash chromatography (30% ethyl acetate in hexanes) to give 3 a whitecrystalline solid (223 mg, 96%). The ee was determined to be 95% byMosher's ester formation and HPLC analysis on a CHIRALCEL OD column,λ=486 nm. Retention times in 10% isopropanol in hexanes were 26.6 min(major) and 39.4 min. R_(f)=0.22 on silica gel (30% ethylacetate:hexanes); mp 128-130° (dec); [α]²⁵ _(D)=70° (c=8.3, CHCl₃); IR(KBr, cm⁻¹) 3462 (br), 3200 (m), 2957 (w), 1447 (m), 1329 (m), 1329 (m),1164 (s), 1093 (m). ¹H NMR (400 MHz, CDCl₃) δ 7.91-7.90 (2H, m),7.62-7.58 (1H, m), 7.54-7.50 (2H, m), 7.47-7.45 (1H, m), 7.27-7.23 (2H,m), 6.40 (1H, dd, J=9.7, 1.7 Hz), 5.55 (1H, dd, J=9.7, 3.1 Hz), 5.26(1H, s), 4.77 (1H, d, J=8.8 Hz), 4.13-4.07 (1H, m), 2.91 (1H, s); ¹³CNMR (400 MHz, CDCl₃) δ 140.2, 134.9, 132.9, 131.3, 129.5, 129.2, 128.4,128.4, 127.1, 126.4, 126.0, 72.0, 56.3. HRMS calcd for C₁₆H₁₅NO₃S (M⁺):301.0773. Found: 301.0769.

(1R*,7R*)-2-Pyrrolidin-1-yl-1,2-dihydro-naplthalen-1-ol (4): To a flamedried round bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.009 mmol), DPPF (9.6mg, 0.017 mmol), pyrrolidine (146 mg, 3.47 mmol), triethylaminehydrochloride (478 mg, 3.47 mmol) and 1 (125 mg, 0.865 mmol) followed byaddition of THF (3 mL) and heating to reflux for 8 hours. The solventwas then removed in vacuo and the resulting mixture purified by flashchromatography (10% methanol in acetone) to give 4 a white crystallinesolid (119 mg, 80° h). R_(f)=0.14 on silica gel (10% methanol inacetone); mp 97-98° (Et₂O); IR (KBr, cm⁻¹) 3496 (br), 3035 (m), 2967(s), 1454 (m), 1193 (s), 1117 (m), 1048 (s). ¹H NMR (400 MHz, CDCl₃) δ7.56 (1H, d, J=7.1 Hz), 7.29-7.21 (2H, m), 7.08-7.06 (1H, m), 6.57 (1H,dd, J=9.9, 2.4 Hz), 6.05 (1H, dd, J=9.9, 2.4 Hz), 4.83 (1H, d, J=11.3Hz), 3.66 (1H, ddd, J=11.3, 2.4, 2.4 Hz), 3.57 (1H, s), 2.81-2.79 (2H,m), 2.73-2.71 (2H, m), 1.84-1.80 (4H, m); ¹³C NMR (400 MHz, CDCl₃) δ136.9, 131.8, 129.6, 127.7, 127.3, 126.1, 125.4, 124.7, 69.8, 63.3,48.7, 23.8. HRMS calcd for C₁₄H₁₇NO (M⁺): 215.1310. Found: 215.1314.

(1R*,2R*)-2-Piperidin-1-yl-1,2-dihydro-napbthalen-1-ol: To a flame driedround bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.0087 mmol), DPPF (9.6 mg,0.0173 mmol), piperidine hydrochloride (422 mg, 3.47 mmol),triethylamine (350 μL, 2.51 mmol) and 1 (100 mg, 0.69 mmol) were addedfollowed by THF (3 mL) and heating to 80° C. for 12 hours. The reactionmixture was then concentrated in vacuo and purified by flashchromatography (50% ethyl acetate, 48% hexanes, 2% methanol) to give 5 awhite crystalline solid (130 mg, 82%). R_(f)=0.24 on silica gel (50%ethyl acetate, 48% hexanes, 2% methanol); mp 62-640 (Et₂O); IR (KBr,cm⁻¹) 3482 (br), 3036 (w), 2937 (s), 2853 (m), 1453 (s), 1193 (s), 1109(s), 1046 (s). ¹H NMR (400 MHz, CDCl₃) δ 7.57 (1H, d, J=7.1 Hz),7.27-7.18 (2H, m), 7.05 (1H, dd, J=6.9, 0.9 Hz), 6.49 (1H, dd, J=9.9,2.6 Hz), 6.12 (1H, dd, J=9.9, 2.4 Hz), 4.87 (1H, d, J=12.2 Hz), 3.58(1H, s), 3.37 (1H, ddd, J=12.2, 2.4, 2.4 Hz), 2.79-2.73 (2H, m), 2.48(2H, m), 1.67-1.57 (4H, m), 1.56-1.46 (2H, m); ¹³C NMR(400 MHz, CDCl₃) δ137.4, 131.8, 128.8, 127.1, 125.9, 125.2, 124.4, 68.2, 67.6, 50.4, 26.5,24.6. HRMS calcd for C₁₅H₁₈NO (M⁺-H): 228.1388. Found: 228.1318.

(1R,2R)-2-(3,4-Dihydro-2H-quinolin-1-yl)-1,2-dihydro-naphthalen-1-ol: Toa flame dried round bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.0087 mmol),(R)-(S)-BPPFA (9.6 mg, 0.0173 mmol), tetrahydroisoquinoline (231 mg,1.735 mmol), 1 (60 mg, 0.416 mmol) and THF (2.5 mL) were added followedby heating to reflux for 3 hours. The solvent was then removed in vacuoand the resulting oil purified by flash chromatography (5% ethyl acetatein hexanes) to give 6 a colourless oil (114.1 mg, 98%). The ee wasdetermined to be 65% using HPLC analysis on a CHIRALCEL OD column, λ=254nm. Retention times in 10% isopropanol in hexanes were 10.3 min (major)and 11.2 min. R_(f)=0.30 on silica gel (10% ethyl acetate:hexanes);[α]²⁵ _(D)=−30.0° (c=13.8, CHCl₃); IR (KBr, cm⁻¹) 3588 (br), 3037 (w),2932 (w), 1601 (s), 1495 (m), 1190 (m). ¹H NMR (400 MHz, CDCl₃) δ7.54-7.52 (1H, m), 7.31-7.29 (2H, m), 7.17-7.14 (1H, m), 7.10-7.09 (1H,m), 7.06-7.04 (1H, m), 6.94-6.93 (1H, m), 6.68-6-67 (1H, m), 6.65 (1H,dd, J=9.4, 2.2 Hz), 5.96 (1H, dd, J=9.9, 3.3 Hz), 5.13 (1H, d, J=8.8Hz), 4.78 (1H, ddd, J=8.8, 2.5, 2.5 Hz);3.31-3.26 (1H, m), 3.14-3.08(1H, m), 2.81-2.80 (2H, m), 2.30 (1H, s), 1.95-1.89 (2H, m); ¹³C NMR(400 MHz, CDCl₃) δ 145.1, 136.5, 131.9, 129.7, 129.5, 128.0, 128.0,128.0, 127.9, 127.0, 126.5, 125.9, 124.0, 116.8, 112.2, 69.5, 60.9,44.1, 28.1, 22.5. HRMS calcd for C₁₉H₁₉NO (M⁺): 277.1467. Found:277.1463.

(1R,2R)-2-(Methyl-phenyl-amino)-1,2-dihydro-naphthalen-1-ol (7): To aflame dried round bottom flask, [Rh(COD)Cl]₂ (3.5 mg, 0.007 mmol),(R)-(S)-BPPFA (7.7 mg, 0.014 mmol), N-methylaniline (372 mg, 3.47 mmol),1 (105 mg, 0.728 mmol) and THF (3 mL) were added followed by heating toreflux for 3 hours. The solvent was then removed in vacuo and theresulting oil purified by flash chromatography (5% ethyl acetate inhexanes) to give 7 a white crystalline solid (176.3 mg, 96%). The ee wasdetermined to be 74% using HPLC analysis on a CHIRALCEL OD column, λ=254nm. Retention times in 10% isopropanol in hexanes were 11.1 min (major)and 13.3 min. R_(f)=0.41 on silica gel (20% ethyl acetate:hexanes); mp55-56° (Et₂O); [α]²⁵ _(D)=50.4° (c=11.8, CHCl₃); IR (KBr, cm⁻¹) 3594(br), 3037 (m), 2884 (m), 1596 (s), 1503 (s), 1463 (m), 1186 (m), 935(m). ¹H NMR (400 MHz, CDCl₃) δ 7.57-7.55 (1H, m), 7.31-7.26 (4H, m),7.15-7.13 (1H, m), 6.99-6.97 (2H, m), 6.84-6.81 (1H, m), 6.61 (1H, dd,J=9.8, 2.6 Hz), 5.94 (1H, dd, J=9.7, 2.9 Hz), 5.11 (1H, d, J=9.8 Hz),4.76 (1H, ddd, J=9.7, 2.6, 2.6 Hz), 2.85 (3H, s), 2.50 (1H, s); ¹³C NMR(400 MHz, CDCl₃) δ 150.1, 136.4, 131.9, 129.6, 129.2, 128.0, 127.8,127.7, 126.4, 125.5, 118.0, 114.5, 70.0, 63.3, 33.3. HRMS calcd forC₁₇H₁₇NO (M⁺): 251.1310. Found: 251.1307.

(1R*,2R*)-2-Benzylamino-1,2-dihydro-naphthalen-1-ol (8): To a flamedried round bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.009 mmol), DPPF (9.6mg, 0.017 mmol), benzylamine hydrochloride (279 mg, 1.74 mmol),triethylamine (242 μL, 1.74 mmol) and 1 (50 mg, 0.347 mmol) followed byaddition of THF (3 mL) and heating to reflux for 3 days. The solvent wasthen removed in vacuo and the resulting mixture purified by flashchromatography (50% ethyl acetate in hexanes) to give 8 a whitecrystalline solid (26.9 mg, 31%). R_(f)=0.44 on silica gel (50% ethylacetate, 48% hexanes, 2% methanol); mp 115-117° (dec) (Et₂O); IR (KBr,cm⁻¹) 3528 (br), 3030 (w), 2849 (w), 1455 (s), 1190 (m), 1112 (m), 1048(m). ¹H NMR (400 MHz, CDCl₃) δ 7.47-7.45 (1H, m), 7.29-7.24 (4H, m),7.24-7.17 (3H, m), 7.02-7.01 (1H, m), 6.41 (1H, dd, J=9.7, 2.0 Hz), 6.00(1H, dd, J=9.7, 2.5 Hz), 4.64 (1H, d, J=9.0 Hz), 3.94 (1H, AB, J=13.0Hz), 3.75 (1H, AB, J=13.0 Hz), 3.42 (1H, ddd, J=11.0, 2.4, 2.4 Hz), 2.44(1H, s); ¹³C NMR (400 MHz, CDCl₃) δ 139.8, 136.6, 132.1, 128.8, 128.5,128.2, 127.9, 127.8, 127.6, 127.2, 126.1, 124.9, 72.1, 59.7, 50.7. HRMScalcd for C₁₇H₁₇NO(M⁺): 251.1310. Found: 251.1316.

(1R*,2R*)-2-(4-Methoxy-benzylamino)-1,2-dihydro-naphthalen-1-ol (9): Toa flame dried round bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.009 mmol),DPPF (9.6 mg, 0.017 mmol), p-methoxybenzylamine (238 mg, 1.74 mmol),triethylamine hydrochloride (239 mg, 1.74 mmol) and 1 (50 mg, 0.728mmol) followed by addition of THF (3 mL) and heating to reflux for 3days. The solvent was then removed in vacuo and the resulting mixturepurified by flash chromatography (50% ethyl acetate in hexanes) to give9 a white crystalline solid (43 mg, 44%). R_(f)=0.27 on silica gel (50%ethyl acetate, 48% hexanes, 2% methanol); mp 96-98° (dec) (Et₂O); IR(KBr, cm⁻¹) 3528 (br), 3033 (w), 2835 (m), 1612 (m), 1512 (s), 1455 (m),1248 (s), 1040 (m). ¹H NMR (400 MHz, CDCl₃) δ 7.52-7.50 (1H, m),7.26-7.22 (4H, m), 7.08-7.06 (1H, m), 6.85 (2H, d, J=9.0 Hz), 6.47 (1H,dd, J=9.7, 2.0 Hz), 6.05 (1H, dd, J=9.9, 2.6 Hz), 4.68 (1H, d, J=11.0Hz), 3.95 (1H, d, J=12.9 Hz), 3.79 (3H, s), 3.75 (1H, d, J=2.9 Hz), 3.46(1H, ddd, J=11.0, 2.4, 2.4 Hz), 3.0-2.0 (2H, s (br)): ¹³C NMR (400 MHz,CDCl₃) δ 158.7, 136.7, 132.1, 131.9, 129.4, 128.9, 127.9, 127.7, 127.5,126.0, 124.9, 113.9, 72.1, 59.6, 55.2, 50.1. HRMS calcd for C₁₈H₁₉NO₂(M⁺): 281.1416. Found: 281.1403.

(1R,2R)-2-Indol-1-yl-1,2-dihydro-naphthalen-1-ol (10): To a flame driedround bottom flask, [Rh(COD)Cl]₂ (4.3 mg, 0.009 mmol), (R)-(S)-BPPFA(9.6 mg, 0.017 mmol), indole (407 mg, 3.47 mmol) and 1 (100 ng, 0.69mmol) were added. THF (4 mL) was then added, followed by heating to 80°C. for 3 days. The reaction mixture was then concentrated in vacuo. Theresulting oil was purified by flash chromatography (30% ethyl acetate inhexanes) to give 10 a colourless oil (147 mg, 81%). The ee wasdetermined to be 79% using HPLC analysis on a CHIRALCEL OD column, λ=254nm. Retention times in 10% isopropanol in hexanes were 28.5 min (major)and 30.1 min. R_(f)=0.26 on silica gel (30% ethyl acetate:hexanes);[α]^(D) ₂₅=−46.7° (c=11.3, CHCl₃); IR (KBr, cm⁻¹) 3485 (br), 3059 (mn),1592 (mn), 1455 (s), 1414 (s), 1245 (mn), 1091 (m), 908 (m); ¹H NMR (400MHz, CDCl₃) δ 8.13 (1H, s), 7.79 (1H, d, J=7.8 Hz), 7.42 (1H, d, J=7.3Hz), 7.34-7.19 (6H, m), 6.85 (1H, d, J=2.2 Hz), 6.69 (1H, dd, J=9.5, 2.0Hz), 6.20 (1H, dd, J=9.5, 3.8 Hz), 5.06 (1H, d, J=7.9 Hz), 4.12-4.08(1H, m), 2.35 (1H, s); ¹³C NMR (400 MHz, CDCl₃) δ 136.5, 135.9, 132.5,130.1, 128.0, 127.7, 126.9, 126.5, 126.4, 126.2, 122.6, 122.0, 119.3,119.2, 113.9, 111.4, 72.7, 41.0. HRMS calcd for C₁₈H₁₅NO (M⁺): 261.1154.Found: 261.1141.

Example 6 Compounds Formed in Reactions Involving Carbon Nucleophiles

(1S*,2R*)-2-(Hydroxy-1,2-dihydro-naphthalen-2-yl)malonic acid dimethylester (2): To a flame dried round bottom flask, [Rh(COD)Cl]₂ (8.6 mg,0.0174 mmol), DPPF (19.2 mg, 0.0347 mmol), dimethyl malonate (137 mg,1.041 mmol) and 1 (100 mg, 0.694 mmol) were added followed by additionof THF (1.5 mL) and heating to 80° C. for 24 hours. The reaction mixturewas then poured in to water and extracted three times with ethylacetate. The organic layers were combined, washed with brine dried overNa₂SO₄, and concentrated in vacuo. The resulting oil was purified byflash chromatography (20% ethyl acetate in hexanes then increasing to50% ethyl acetate in hexanes) to give 2 a colourless oil whichcrystallized on sitting (124.3 mg, 65%). R_(f)=0.27 on silica gel (50%ethyl acetate:hexanes); mp 65-67° (Et₂O); IR (neat, cm⁻¹) 3490 (br),3024 (m), 2954 (s), 1744 (s), 1436 (s), 1159 (s), 1026 (s), 913 (m), 783(s); ¹H NMR (400 MHz, CDCl₃) δ 7.40-7.38 (1H, m), 7.30-7.24 (2H, m),7.13-7.11 (1H, m), 6.57 (1H, dd, J=9.7, 1.5 Hz), 5.97 (1H, dd, J=9.7,4.2 Hz), 4.70 (1H, dd, J=6.2, 6.2 Hz), 3.73 (3H, s), 3.70 (3H, s), 3.52(1H, d, J=7.6 Hz), 3.37-3.35 (1H, m), 2.09 (1H, d, J=6.2 Hz); ³C NMR(400 MHz, CDCl₃) δ 168.6, 168.3, 135.4, 131.9, 128.3, 128.1, 126.8,126.7, 70.3, 52.6, 52.6, 52.5, 42.3l . HRMS calcd for C₁₅H₁₆O₅ (M⁺):276.0998. Found: 276.0104.

Example 7 Compounds Formed in Reactions Involving Phenol Nucleophiles

(1S,2S)-2-Phenoxy-1,2-dihydro-naphthalen-1-ol (2): To a flame driedround bottom flask, [Ph(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0069 mmol, and 1 (100 m, 0.694 mmol)were added. THF (2 mL) and phenol (327 mg, 3.47 mmol) were then addedfollowed by heating to 80° C. for 1.5 hours. The reaction mixture wasthen poured in to ether and washed three times with 5% aqueous Noah. Theaqueous layers were combined and back extracted three times with ether.The organic layers were combined, washed with brine, dried over Na₂SO₄,and concentrated in vacuo. The resulting solid was purified by flashchromatography (20% ethyl acetate in hexanes) to give 2 as a whitecrystalline solid (130.7 mg, 83%). The ee was determined to be 99.2%using HPLC analysis on a CHIRALCEL OD column, λ=486 nm. Retention timesin 4% isopropanol in hexanes were 15.2 min (major) and 17.8 min.F_(r)=0.26 on silica gel (10% ethyl acetate:hexanes); mp 109-110° C.(Et₂O); [α]²⁵ _(D)=+204.7° (c=10.1, CHCl₃); IR (KBr, cm⁻¹) 3337 (br),3029 (w), 2866 (w), 1600 (m), 1496 (s), 1249 (s), 1062 (s); ¹H NMR (400MHz, CDCl₃) δ 7.65-7.63 (1H, m), 7.33-7.25 (4H, m), 7.13-7.11 (1H, m),7.01-6.95 (3H, m), 6.51 (1H, dd, J=9.9, 1.6 Hz), 6.02 (1H, dd, J=9.9,2.2 Hz), 5.19 (1H, d, J=10.4 Hz), 5.11 (1H, ddd, J=10.4, 2.0, 2.0 Hz),2.66 (1H, s); ¹³C NMR (400 MHz, CDCl₃) δ 157.4, 135.5, 131.9, 129.7,129.0, 128.2, 128.0, 126.4, 126.1, 125.2, 121.5, 115.9, 79.1, −72.4.HRMS calcd for C₁₆H₁₄O₂ (M⁺): 238.0994. Found: 238.0984.

(1S,2S)-2-(4-nitrophenoxy)-1,2,-dihydro-naphthalen-1-ol (3): To a flamedried round-bottomed flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0069 mmol) and 1 (100 mg, 0.694 mmol)were added followed by addition of THF (2.5 mL) and 4-nitrophenol (483mg, 3.47 mmol). The mixture was heated at 80° C. for 45 minutes, thenpoured into diethyl ether and extracted 3 times with 10% aqueous sodiumhydroxide solution. The aqueous extracts were combined andback-extracted three times with diethyl ether. The combined etherextracts were washed with brine and dried with anhydrous sodium sulfate.The solvents were removed in vacuo, yielding a solid which was purifiedby flash chromatography on silica gel (30% ethyl acetate in hexanes)giving a white crystalline solid 3 (184 mg, 94%). The ee was determinedto be 97% by formation of Mosher's ester. F_(r)=0.43 on silica (30%ethyl acetate:hexanes); mp 123-125° C. (dec.); [α]²⁵ _(D)=+169.9°(c=10.3, CHCl₃); IR (KBr, cm⁻¹) 3351 (br), 3113 (w), 3071 (w), 2884 (w),2843 (w), 1591 (s), 1503 (s), 1342 (s), 1295 (m), 1110 (m), 896 (w); ¹HNMR (400 MHz, CDCl₃): δ 8.18 (2H, d, J=9.2 Hz), 7.62-7.60 (1H, m),7.31-7.29 (2H, m), 7.15-7.13 (1H, m), 6.99 (2H, d, J=9.2 Hz), 6.57 (1H,d, J=9.9 Hz), 5.94 (1H, d, J=9.9 Hz), 5.20 (2H, s), 2.61 (1H, s); ¹³CNMR(400 MHz, CDCl₃): δ 162.6, 141.8, 135.0, 131.5, 130.2, 128.5, 128.4,126.8, 126.0, 125.5, 124.1, 115.4, 79.6, 72.0.

(1S,2S)-2-(4-Cyanophenoxy)-1,2,-dihydro-naphthalen-1-ol (4): To a flamedried round-bottomed flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0069 mmol) and 1 (100 mg, 0.694 mmol)were added followed by addition of THF (2.5 mL) and 4-cyanophenol (413mg, 3.47 mmol). The mixture was heated at 80° C. for 5 hours, thenpoured into diethyl ether and extracted 3 times with 10% aqueous sodiumhydroxide solution. The aqueous extracts were combined andback-extracted three times with diethyl ether. The combined etherextracts were washed with brine and dried with anhydrous sodium sulfate.The solvents were removed in vacuo, yielding a solid which was purifiedby flash chromatography on silica gel (30% ethyl acetate in hexanes)giving a white crystalline solid 4 (160 mg, 88%). The ee was determinedto be 97% by HPLC analysis on a CHIRALCEL OD column, λ=256 nm. Retentiontimes in 3% isopropanol in hexanes were 35.3 min and 37.7 min (major).F_(r)=0.40 on silica (30% ethyl acetate in hexanes); mp 140-141° C.(Et₂O); [α]²⁵ _(D)=+182.3° (c=11.2, CHCl₃) IR (KBr, cm⁻¹) 3303 (b) 3050(w) 2210 (m) 1598 (s) 1503 (s) 1238 (s) 1025 (m) 859 (m) 778 (m); ¹H NMR(400 MHz, CDCl₃): δ 7.62-7.57 (3H, m), 7.33-7.27 (3H, m), 7.14-7.12 (1H,m), 6.56 (1H, dd, J=1.4, 9.7 Hz), 5.93 (1H, dd, J=1.4, 9.7 Hz),5.20-5.13 (2H, m), 2.25 (1H, s). ¹³C NMR (400 MHz, CDCl₃): δ 160.8,135.0, 134.2, 131.5, 130.0, 128.5, 128.3, 126.7, 125.4, 124.4, 119.0,116.2, 104.6, 79.2, 72.0. HRMS calcd for (M-H₂O)⁺ (C₁₇H₁₁ON): 245.0841.Found: 245.0845.

(1S,2S)-2-(4-acylphenoxy)-1,2,-dihydro-naphthalen-1-ol (5): To a flamedried round-bottomed flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0069 mmol) and 1 (100 mg, 0.694 mmol)were added followed by addition of THF (2.5 mL) and4-hydroxyacetophenone (472 mg, 3.47 mmol). The mixture was heated at 80°C. for 2.5 hours, then poured into diethyl ether and extracted 3 timeswith 10% aqueous sodium hydroxide solution. The aqueous extracts werecombined and back-extracted three times with diethyl ether. The combinedether extracts were washed with brine and dried with anhydrous sodiumsulfate. The solvents were removed in vacuo, yielding a solid which waspurified by flash chromatography on silica gel (30% ethyl acetate inhexanes) giving a white crystalline solid 5 (177 mg, 91%). The ee wasdetermined to be >99% by formation of Mosher's ester; R_(f)=0.28 onsilica (30% ethyl acetate in hexanes); mp 124-126° C. (Et₂O); [α]²⁵_(D)=+153° (c=9.8, CHCl₃). IR (KBr, cm⁻¹) 3367 (b), 3069 (w), 2916 (w),1668 (s), 1601 (s), 1265 (s), 1053 (m), 835 (m), 779 (m); ¹H NMR (400MHz, CDCl₃): δ 7.94 (2H, d, J=8.8 Hz), 7.66-7.64 (1H, m), 7.34-7.27 (2H,m), 7.16-7.14 (1H, m), 6.98 (2H, d, J=8.8 Hz), 6.57 (1H, d, J=9.9 Hz),5.99 (1H, d, J=9.9 Hz), 5.21 (2H, s), 2.85 (1H, s), 2.56 (3H, s); ¹³CNMR (400 MHz, CDCl₃): δ 196.8, 161.4, 135.3, 131.7, 130.7, 130.6, 129.6,128.3, 128.1, 126.6, 125.4, 125.0, 115.2, 79.0, 72.0, 26.3. HRMS calcdfor (M-H₂O)⁺ (C₁₈H₁₄O₂): 262.0994. Found: 262.0989.

(1S,2S)-2-(4-Trifluoromethylphenoxy)-1,2,-dihydro-naphthalen-1-ol (6):To a flame dried round-bottomed flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035mmol), (S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0069 mmol) and 1 (100 mg, 0.694mmol) were added followed by addition of THF (2.5 mL) and4-trifluoromethylphenyl (563 mg, 3.47 mmol). The mixture was heated at80° C. for 8 hours, then poured into diethyl ether and extracted 3 timeswith 10% aqueous sodium hydroxide solution. The aqueous extracts werecombined and back-extracted three times with diethyl ether. The combinedether extracts were washed with brine and dried with anhydrous sodiumsulfate. The solvents were removed in vacuo, yielding a solid which waspurified by flash chromatography on silica gel (10% ethyl acetate inhexanes) to give a white crystalline solid 6 (184 mg, 87%). The ee wasdetermined to be 95% by HPLC analysis on a CHIRALCEL OD column, λ=486nm. Retention times in 4% isopropanol in hexanes were 14.8 min and 17.3min (major). R_(f)=0.46 on silica (20% ethyl acetate in hexanes); mp118-119° C. (Et₂O); [α]²⁵ _(D)=+1780 (c=9.6, CHCl₃). IR (KBr, cm¹) 3360(br), 3061 (w), 2874 (w), 1617 (m), 1518 (m), 1326 (s), 1103 (s), 1051(m), 839 (m), 782 (m), 745 (w); ¹H NMR (400 MHz, CDCl₃): δ 7.63-7.54(1H; m), 7.55 (2H, d, J=8.6 Hz), 7.33-7.24 (2H, m), 7.14-7.12 (1H, m),7.01 (2H, d, J=8.6 Hz), 6.55 (1H, dd, J=1.6, 9.9 Hz), 5.97 (1H, dd,J=2.0, 9.9 Hz), 5.21-5.13 (2H, m), 2.47 (1H, d, J=3.6 Hz); ¹³C NMR (400MHz, CDCl₃): δ 159.9, 135.2, 131.7, 129.6, 128.4, 128.2, 127.1 (q,J^(C−F)=3.6 Hz), 126.6, 125.4, 124.9, 123.4 (d, J^(C−F)=33.0 Hz), 122.9(d, J^(C−F)=271.6 Hz), 115.6, 79.1, 72.1; HRMS calcd for (M⁺)(C₁₇H₁₃O₂F₃): 306.0868. Found: 306.0852.

(1S,2S)-2-(4-Fluorophenoxy)-1,2,-dihydro-naphthalen-1-ol (7): To a flamedried round-bottomed flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0069 mmol) and 1 (100 mg, 0.694 mmol)were added followed by addition of THF (2.5 mL) and 4-fluorophenol (389mg, 3.47 mmol). The mixture was heated at 80° C. for 5 hours, thenpoured into diethyl ether and extracted 3 times with 10% aqueous sodiumhydroxide solution. The aqueous extracts were combined andback-extracted three times with diethyl ether. The combined etherextracts were washed with brine and dried with anhydrous sodium sulfate.The solvents were removed in vacuo, yielding a solid which was purifiedby flash chromatography on silica gel (10% ethyl acetate in hexanes)giving a white crystalline solid 7 (163 mg, 92%). The ee was determinedto be 97% by HPLC analysis on a CHIRALCEL OD column, λ=486 nm).Retention times in 1.5% isopropanol in hexanes were 28.1 min (major) and29.5 min. R_(f)=0.39 on silica (20% ethyl acetate in hexanes); mp127-129° C. (Et₂O); [α]²⁵ _(D)=+216° (c=9.5, CHCl₃). IR (KBr, cm⁻¹) 3309(b), 3071 (w), 2864 (w), 1504 (s), 1284 (m), 1052 (s), 781 (s), 692 (m);¹H NMR (400 MHz, CDCl₃): δ 7.63-7.61 (1H, m), 7.31-7.26 (2H, m),7.12-7.10 (1H, m), 7.00-6.95 (2H, m), 6.92-6.88 (2H, m), 6.51 (1H, dd,J=2.1, 9.9 Hz), 5.98 (1H, dd, J=2.2, 9.9 Hz), 5.15 (1H, dd, J=3.6, 10.0Hz), 5.01 (1H, ddd, J=2.1, 2.1, 10.1 Hz), 2.54 (1H, d, J=3.8 Hz); ¹³CNMR (400 MHz, CDCl₃): δ 157.6 (d, J^(C−F)=239 Hz), 156.4, 153.4, 135.4,131.8, 129.1, 128.2, 126.5, 125.7, 125.2, 117.5 (d, J^(C−F)=8 Hz), 116.1(d, J^(C−F)=23.5 Hz);. HRMS calcd for (M⁺) (C₁₆H₁₃O₂F): 256.0810. Found:256.0911.

(1S,2S)-2-(4-Chlorophenoxy)-1,2,-dihydro-naphthalen-1-ol (8): To a flamedried round-bottomed flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0069 mmol) and 1 (100 mg, 0.694 mmol)were added followed by addition of THF (2.5 mL) and 4-chlorophenol (446mg, 3.47 mmol). The mixture was heated at 80° C. for 6 hours, thenpoured into diethyl ether and extracted 3 times with 10% aqueous sodiumhydroxide solution. The aqueous extracts were combined andback-extracted three times with diethyl ether. The combined etherextracts were washed with brine and dried with anhydrous sodium sulfate.The solvents were removed in vacuo, yielding a solid which was purifiedby flash chromatography on silica gel (5% ethyl acetate in hexanes)giving a white crystalline solid 8 (169 mg, 89%). The ee was determinedto be 92% by formation of Mosher's ester. R_(f)=0.47 on silica (20%ethyl acetate in hexanes); mp 125-125.5° C. (Et₂O); [α]²⁵ _(D)=+150°(c=10.6, CHCl₃). IR (KBr, cm⁻¹) 3302 (br), 3064 (w), 2874 (w), 1590 (m),1489 (s), 1362 (w), 1230 (s), 1052 (m), 890 (w), 846 (m), 778 (s), 663(m); ¹H NMR (400 MHz, CDCl₃): δ 7.65-7.64 (1H, m), 7.33-7.26 (4H, m),7.16-7.13 (1H, m), 6.91(1H, ddd, J=2.0, 2.0, 8.9 Hz), 6.55 (1H, dd,J=1.8, 9.9 Hz), 5.99 (1H, dd, J=2.2, 9.9 Hz), 5.19 (1H, dd, J=3.8, 10.0Hz), 5.07 (1H, ddd, J=2.0, 2.0, 10.1 Hz), 2.56 (1H, d, J=4.0 Hz); ¹³CNMR (400 MHz, CDCl₃): δ 155.8, 135.2, 131.7, 129.5, 129.3, 128.2, 128.1,126.5, 126.2, 125.3, 125.2, 116.9, 79.2, 72.1. HRMS calcd for (M-H₂O)⁺(C₁₆H₁₁OCl): 254.0498. Found: 254.0499.

(1S,2S)-2-(4-Iodophenoxy)-1,2,-dihydro-naphthalen-1-ol (9): To a flamedried round-bottomed flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0669 mmol) and 1 (100 mg, 0.694 mmol)were added followed by addition of THF (2.5 mL) and 4-iodophenol (763mg, 3.47 mmol). The mixture was heated at 80° C. for 12 hours, thenpoured into diethyl ether and extracted 3 times with 10% aqueous sodiumhydroxide solution. The aqueous extracts were combined andback-extracted three times with diethyl ether. The combined etherextracts were washed with brine and dried with anhydrous sodium sulfate.The solvents were removed in vacuo, yielding a solid which was purifiedby flash chromatography on silica gel (10% ethyl acetate in hexanes) asa white crystalline solid 9 (193 mg, 73%). The ee was determined bydeiodinating 9 (40 m; 0.11 mmol) by reaction with t-BuLi (0.32 mL, 1.7M)in diethyl ether (2 mL) at −78° C. followed by quenching withisopropanol. Extraction with ether from water, washing with brine,drying over anhydrous sodium sulfate and removal of the solvents invacuo gave a white crystalline solid (24 mg, 92%). The ee was determinedto be 98% by HPLC analysis on a CHIRALCEL OD column, λ=256 nm. Retentiontimes in 4% isopropanol in hexanes were 15.2 min (major) and 17.9 min;R_(f)=0.44 on silica (20% ethyl acetate in hexanes); mp 160-162° C.(Et₂O); [α]²⁵ _(D)=+107° (c=9.7, CHCl₃). IR (KBr, cm⁻¹) 3264 (br), 3050(w), 2926 (w), 2843 (w), 1581 (m), 1485 (s), 1388 (w), 1279 (m), 1246(s), 1046 (m), 824 (m), 780 (m), 571 (w); ¹H NMR (400 MHz, CDCl₃): δ7.63-7.61 (1H, m). 7.58-7.55 (2H, m), 7.30-7.27 (2H, m), 7.13-7.11 (1H,m), 6.73 (2H, ddd, J=2.2, 2.2, 9.0 Hz), 6.52 (1H, dd, J=1.8, 9.8 Hz),5.96 (1H, dd, J=2.2, 9.8 Hz), 5.16 (1H, d, J=10.0 Hz), 5.05 (1H, ddd,J=2.0, 2.0, 10.0 Hz), 2.54 (1H, s); ¹³C NMR (400 MHz, CDCl₃): δ 157.3,138.5, 135.3, 131.7, 129.4, 128.3, 128.1, 126.6, 125.3, 125.3, 118.1,83.6, 79.2, 72.2. HRMS calcd for (M-H₂O)⁺ (C₁₆H₁₁OI): 345.9855. Found:345.9849.

(1R,2R)-2-(4-Bromo-phenoxy)-1,2-dihydro-naphthalen-1-ol: To a flamedried round bottom flask, [Rh(COD)Cl]₂ (2.1 mg, 0.0043 mmol),(R)-(S)-PPF-P^(t)Bu₂ (4.6 mg, 0.0085 mmol, and 1 (122 mg, 0.85 mmol)were added.). THF (2 mL) and p-bromophenol (734 mg, 4.245 mmol) werethen added followed by heating to 80° C. for 1.5 hours. The reactionmixture was then poured in to ether and washed three times with 5%aqueous NaOH. The aqueous layers were combined and back extracted threetimes with ether. The organic layers were combined, washed with brine,dried over Na₂SO₄, and concentrated in vacuo. The resulting solid waspurified by flash chromatography (20% ethyl acetate in hexanes) to give10 a white crystalline solid (239.7 mg, 90%). The ee was determined bydebrominating 10 (44 mg, 0.139 mmol) by reaction with t-BuLi (0.2 mL,1.7M) in ether (2 mL) at −78° C. followed by quenching with isopropanol.Extraction with ether from water, washing with brine, drying over Na₂SO₄and concentration gave a white crystalline solid 2 (31.5 mg, 95%). Theee was determined to be 96.8% by HPLC analysis on a CHIRALCEL OD column,λ=486 nm. Retention times in 4% isopropanol in hexanes were 15.2 min and17.5 min (major). R_(f)=0.26 on silica gel (10% ethyl acetate:hexanes);mp 145-146° (Et₂O); [α]²⁵ _(D)=−135.70 (c=10.2, CHCl₃); IR (KBr, cm⁻¹)3290 (br), 3060 (m), 2870 (w), 1583 (m), 1484 (s), 1227 (s), 1052 (m),980 (s), 776 (s); ¹H NMR (400 MHz, CDCl₃) δ 7.70-7.65 (1H, m), 7.44-7.42(2H, m), 7.35-7.32 (2H, m), 7.18-7.16 (1H, m), 6.88-6.86 (2H, m), 6.56(1H, dd, J=10.0, 2.0 Hz), 6.00 (1H, dd, J=9.7, 2.2 Hz), 5.20 (1H, dd,J=9.7, 3.6 Hz), 5.09 (1H, ddd, J=10.0, 2.0, 2.0 Hz), 2.70 (1H, d, J=3.9Hz); ¹³C NMR (400 MHz, CDCl₃) δ 156.5, 135.3, 132.5, 131.7, 129.3,128.3, 128.1, 126.5, 125.3, 117.6, 113.7, 79.4, 72.2. HRMS calcd forC₁₆H₁₁OBr (M-H₂O)⁺ 297.9994. Found: 297.9995.

(1S,2S)-2-(4-Methylphenoxy)-1,2,-dihydro-naphthalen-1-ol (11): To aflame dried round-bottomed flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0069 mmol) and 1 (50 mg, 0.347 mmol)were added followed by addition of THF (2.5 mL) and p-cresol (188 mg,1.74 mmol). The mixture was heated at 80° C. for 24 hours, then pouredinto diethyl ether and extracted 3 times with 10% aqueous sodiumhydroxide solution. The aqueous extracts were combined andback-extracted three times with diethyl ether. The combined etherextracts were washed with brine and dried with anhydrous sodium sulfate.The solvents were removed in vacuo, yielding a solid which was purifiedby flash chromatography on silica gel (5% ethyl acetate in hexanes)giving a white crystalline solid 11 (57 mg, 65%). The ee was determinedto be 91% by HPLC analysis on a CHIRALCEL OD column, λ=256 nm. Retentiontimes in 1% isopropanol in hexanes were 33.8 min (major) and 37.1 min.R_(f)=0.49 on silica (20% ethyl acetate in hexanes); mp 80-81° C.(Et₂O); [α]²⁵ _(D)=+145° (c=12.1, CHCl₃). IR (KBr, cm⁻¹) 3303 (br), 3050(w), 2210 (m), 1598 (s), 1503 (s), 1238 (s), 1025 (m), 859 (m), 778 (m);¹H NMR (400 MHz, CDCl₃): δ 7.67-7.65 (1H, m), 7.33-7.28 (2H, m),7.14-7.11 (3H, m), 6.88 (2H, d, J=8.4 Hz), 6.51 (1H, dd, J=1.8, 9.9 Hz),6.04 (1H, dd, J=2.0, 9.9 Hz), 5.20 (1H, dd, J=1.6, 10.2 Hz), 5.09 (1H,ddd, J=1.8, 1.8, 10.2 Hz), 2.87 (1H, d, J=2.7 Hz), 2.33 (3H, s). ¹³C NMR(400 MHz, CDCl₃): δ 155.0, 135.4, 131.8, 130.7, 130.1, 128.8, 128.1,127.9, 126.4, 126.2, 125.1, 115.6, 79.0, 72.3, 20.5. HRMS calcd for (M⁺)(C₁₇H₁₆O₂): 252.1150. Found: 252.1140.

(1S,2S)-2-(4-Methoxyphenoxy)-1,2,-dihydro-naphthalen-1-ol (12): To aflame dried round-bottomed flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (3.8 mg, 0.0069 mmol) and 1 (100 mg, 0.694 mmol)were added followed by addition of THF (2.5 mL) and 4-methoxyphenol (431mg, 3.47 mmol). The mixture was heated at 80° C. for 6 hours, thenpoured into diethyl ether and extracted 3 times with 10% aqueous sodiumhydroxide solution. The aqueous extracts were combined andback-extracted three times with diethyl ether. The combined etherextracts were washed with brine and dried with anhydrous sodium sulfate.The solvents were removed in vacuo, yielding a solid which was purifiedby flash chromatography on silica gel (10% ethyl acetate in hexanes) asa white crystalline solid 12 (159 mg, 85%). The ee was determined to be95% by HPLC analysis on a CHIRALCEL OD column, λ=256 nm. Retention timesin 4% isopropanol in hexanes were 22.1 min (major) and 25.9 min.R_(f)=0.33 on silica (20% ethyl acetate in hexanes); mp 91-92° C.(Et₂O); [α]²⁵ _(D)=+129° (c=9.9, CHCl₃); IR (KBr, cm⁻¹) 3349 (br), 3050(w), 2822 (w), 1508 (s), 1233 (s), 1046 (m), 825 (m), 751 (m), 695 (w);¹H NMR (400 MHz, CDCl₃): δ 7.66-7.64 (1H, m), 7.30-7.27 (2H, m),7.12-7.10 (1H, m), 6.91 (2H, ddd, J=2.3, 2.3, 9.1 Hz), 6.84 (2H, ddd,J=2.4, 2.4, 9.2 Hz), 6.49 (1H, dd, J=2.0, 9.9 Hz), 6.02 (1H, dd, J=2.4,9.9 Hz), 5.17 (1H, dd, J=3.3, 10.1 Hz), 5.02 (1H, ddd, J=2.0, 2.0, 10.3Hz), 3.77 (3H, s), 3.12 (1H, d, J=3.4 Hz). ¹³C NMR (400 MHz, CDCl₃): δ154.3, 151.2, 135.5, 131.9, 128.7, 128.1, 127.9, 126.4, 126.3, 125.2,117.2, 114.8, 80.0, 72.4, 55.7. HRMS calcd for (M⁺) (C₁₇H₁₄O₂):250.0994. Found: 250.1006.

(1S,2S)-2-(2-Bromophenoxy)-1,2,-dihydro-naphthalen-1-ol (13): To a flamedried round-bottomed flask, [Rh(COD)Cl]₂ (1.7 mg, 0.0035 mmol),(S)-(R)-PPF-P^(t)Bu₂ (38 mg, 0.0069 mmol) and 1 (100 mg, 0.694 mmol)were added followed by addition of THF (2.5 mL) and 2-bromophenol (0.40mL, 3.47 mmol). The mixture was heated at 80° C. for 24 hours, thenpoured into diethyl ether and extracted 3 times with 10% aqueous sodiumhydroxide solution. The aqueous extracts were combined andback-extracted three times with diethyl ether. The combined etherextracts were washed with brine and dried with anhydrous sodium sulfate.The solvents were removed in vacuo, yielding a solid which was purifiedby flash chromatography on silica gel (5% ethyl acetate in hexanes) as awhite crystalline solid 13 (75 mg, 37%). The ee was determined to be 81%by HPLC analysis on a CHIRALCEL OD column, λ=486 nm. Retention times in1.5% isopropanol in hexanes were 22.8 min and 32.1 min (major).R_(f)=0.44 on silica (20% ethyl acetate in hexanes); mp 120-122° C.(Et₂O); [α]²⁵ _(D)=+2540 (c=9.2, CHCl₃). IR (KBr, cm⁻¹) 3341 (br), 3071(w), 2884 (w), 1581 (m), 1472 (s), 1358 (m), 1237 (s), 1028 (s), 987(s), 780 (s), 689 (m), 569 (m); ¹H NMR (400 MHz, CDCl₃): δ 7.67 (1H, dJ=6.8 Hz), 7.58 (1H, dd, J=1.5, 7.9 Hz), 7.33-7.23 (3H, m), 7.14-7.12(1H, m), 6.95(1H, dd, J=1.1, 8.2 Hz), 6.92-6.87 (1H, m), 6.52 (1H, dd,J=2.0, 9.9 Hz), 6.06 (1H, dd, J=1.8, 9.9 Hz), 5.32 (1H, d, J=11.0 Hz),5.10 (1H, ddd, J=2.0, 2.0, 11.0 Hz), 2.85 (1H, d, J=3.2 Hz). ¹³C NMR(400 MHz, CDCl₃): δ 154.3, 135.4, 133.6, 131.8, 129.1, 128.6, 128.3,128.0, 126.4, 126.0, 124.9, 122.9, 115.6, 113.5, 82.2, 72.5. HRMScalculated for (M-H₂O)⁺ (C₁₆H₁₁OBr): 297.9993. Found: 297.9976.

II. Compounds Made Using Azabicyclics

Example 8 Azabicyclic Starting Materials

Example 9 Compounds Formed in Reactions Involving Alcohols

To a round bottomed flask was added 1 (44 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (1 ml) and MeOH(1 ml) were then added and the solution heated to reflux for 6 hours.The reaction mixture was then concentrated and chromatographed to give 6(28 mg, 56%) a colourless oil. ¹H NMR (400 MHz, CDCl₃) δ 7.35 (1H, d,J=7.2 Hz), 7.28-7.13 (4H, m), 6.76-6.68 (4H, m), 6.64 (1H, d, J=9.9 Hz),6.11 (1H, dd, J=4.0, 9.7 Hz), 5.73 (1H, d, J=6.0 Hz), 4.21 (1H, dd,J=4.3, 4.3 Hz), 3.82 (1H, s), 3.42 (3H, s); ¹³C NMR (400 MHz, CDCl₃) δ147.1, 135.2, 132.0, 129.9, 129.4, 129.3, 128.4, 128.3, 128.1, 127.0,126.5, 126.5, 75.8, 56.1, 55.8. HRMS calcd for C₁₇H₁₇NO (M⁺): 251.1310.Found: 251.1315.

To a round bottomed flask was added 2 (49 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (1 ml) and MeOH(1 ml) were then added and the solution heated to reflux for 48 hours.The reaction mixture was then concentrated and chromatographed (10%ethyl acetate:hexanes) to give 7 (41 mg, 74%) a white solid. Theregiochemistry and relative stereochemistry was proven by X-ray crystaldiffraction. R_(f)=0.25 on silica gel (10% ethyl acetate:hexanes); ¹HNMR (400 MHz, CDCl₃) δ 7.35-7.34 (1H, m), 7.25-7.20 (2H, m), 7.10-7.08(1H, m), 6.58 (2H, d, J=9.7 Hz), 6.07 (1H, dd, J=4.3, 9.7 Hz), 4.98 (1H,dd, J=5.5, 8.0 Hz), 4.61 (1H, d, J=7.7 Hz), 4.00 (1H, dd, J=4.6, 4.6Hz), 3.45 (3H, s), 1.44 (9H, s); ¹³C NMR (400 MHz, CDCl₃) δ 155.3,134.1, 131.9, 130.0, 130.0, 128.3, 128.3, 127.0, 125.9, 79.6, 56.3,51.3, 28.4. HRMS calcd for C₁₆H₂₁NO₃ (M⁺): 275.1521. Found: 275.1518.

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (1 ml) and MeOH(1 ml) were then added and the solution heated to reflux for 9 hours(Note: 3 and 8 nearly co-spot by TLC but 8 stains red with permanganatewhereas 3 stains white). The reaction mixture was then concentrated andchromatographed to give 8 (60 mg, 91%) a crystalline solid. mp 128-129°C.; ¹H NMR (400 MHz, CDCl₃) δ 7.78 (2H, d, J=8.0 Hz), 7.33 (2H, d, J=7.9Hz), 7.25-7.18 (1H, m), 7.11-7.04 (2H, m), 6.80 (2H, d, J=7.5 Hz), 6.60(1H, d, J=9.7 Hz), 6.06 (1H, dd, J=5.1, 9.2 Hz), 4.50 (2H, s (br)), 3.98(1H, s), 2.29 (3H, s), 2.47 (3H, s); ¹³C NMR (400 MHz, CDCl₃) δ 144.9,137.2.132.4, 131.7, 130.3, 129.6, 128.8, 128.4, 127.3, 124.9, 77.2,56.5, 54.1, 21.6. Anal. Calcd for C₁₈H₁₉NO₃S: C, 65.63; H, 5.81; N,4.25. Found: C, 65.74; H, 5.89; N, 4.19.

To a round bottomed flask was added 5 (61 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (1 ml) and MeOH(1 ml) were then added and the solution heated to reflux for 6 hours.The reaction mixture was then concentrated and chromatographed to give 9(53 mg, 78%) a colourless oil. ¹H NMR (400 MHz, CDCl₃) δ 7.51-7.47 (1H,m), 7.30-7.24 (2H, m), 7.14-7.10 (1H, m), 6.59 (1H, d, J=9.9 Hz), 6.10(1H, dd, J=3.7, 9.9 Hz), 5.41(1H, dd, J=8.8, 8.8 Hz), 4.55 (1H, d, J=8.8Hz), 4.06 (1H, dd, J=3.6, 6.9 Hz), 3.45 (3H, s), 3.04-2.95 (2H, m),1.07-0.85 (2H, m), 0.03 (6H, s); ¹³C NMR (400 MHz, CDCl₃) δ 133.7,131.9, 129.9, 128.7, 128.4, 127.7, 127.2, 125.5, 77.3, 56.5, 55.5, 50.2,10.5, −2.0. HRMS calcd for C₁₆H₂₅NO₃SSi (M⁺): 339.1324. Found: 339.1327.

Example 10 Compounds Formed in Reactions Involving Phenol Nucleophiles

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (2 ml) and PhOH(94 mg, 1.0 mmol) were added and the solution heated to reflux for 12hours. The reaction mixture was then concentrated and chromatographed togive 10 (63 mg, 81%) a crystalline solid. ¹H NMR (400 MHz, CDCl₃) δ 7.72(2H, d, J=8.2 Hz), 7.30-7.20 (5H, m), 7.14-7.09 (2H, m), 6.98-6.92 (1H,m), 6.87 (1H, d, J=7.4 Hz), 6.77 (2H, d, J=8.4 Hz), 6.64 (1H, d, J=10.2Hz), 6.06 (1H, dd, J=4.6, 9.2 Hz), 5.00 (1H, dd, J=4.7, 4.7 Hz),4.71-4.64 (2H, m), 2.44 (3H, s); ¹³C NMR (400 MHz, CDCl₃) δ 156.8,143.6, 137.5, 132.5, 131.7, 130.9, 129.7, 129.5, 128.9, 128.6, 128.2,127.4, 127.4, 124.2, 121.4, 115.9, 73.2, 54.4, 21.5. Anal. Calcd forC₂₃H₂₁NO₃S: C, 70.56; H, 5.41; N, 3.58. Found: C, 70.58; H, 5.43; N,4.18.

Example 11 Compounds Formed in Reactions Involving Nitrogen or CarbonNucleophiles

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (2 ml) andN-methylaniline (107 mg, 1.0 mmol) were added and the solution heated toreflux for 8 hours. The reaction mixture was then concentrated andchromatographed to give 11 (72 mg, 89%) a crystalline solid. mp 136-142°C.; ¹H NMR (400 MHz, CDCl₃) δ 7.62 (2H, d, J=8.1 Hz), 7.26-7.18 (4H, m),7.14-7.08 (2H, m), 6.90 (1H, d, J=7.3 Hz), 6.80-6.68 (4H, m), 5.86 (1H,dd, J=4.6, 9.9 Hz), 4.73-4.53 (2H, m), 2.42 (3H, s), 2.34 (3H, s); ¹³CNMR (400 MHz, CDCl₃) δ 148.9, 143.4, 137.5, 133.7, 132.2, 130.4, 129.6,129.2, 128.7, 128.4, 127.7, 127.3, 127.0, 126.0, 117.6, 113.8, 58.9,54.6, 32.3, 21.5. Anal. Calcd for C₂₄H₂₄N₂O₂S: C, 71.26; H, 5.98; N,6.93. Found: C, 71.32; H, 6.01; N, 4.16.

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (2 ml) andtetrahydroquinoline (133 mg, 1.0 mmol) were added and the solutionheated to reflux for 9 hours. The reaction mixture was then concentratedand chromatographed to give 12 (63 mg, 73%) a crystalline solid. mp135-137° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.63 (2H, d, J=8.2 Hz), 7.25-7.20(1H, m), 7.18 (2H, d, J=8.2 Hz), 7.11-7.00 (3H, m), 6.90 (1H, d, J=6.4Hz), 6.83 (2H, d, J=7.9 Hz), 6.71 (1H, d, J=9.7 Hz), 6.64-6.58 (1H, m),5.84 (1H, dd, J=5.0, 9.7 Hz), 4.83 (1H, d, J=8.1 Hz), 4.66 (1H, dd,J=4.6, 4.6 Hz), 4.58 (1H, dd, J=4.7, 7.8 Hz), 3.00-2.94 (1H, m),2.62-2.40 (3H, m), 2.41 (3H, s), 1.60-1.52 (2H, m); ¹³C NMR (400 MHz,CDCl₃) δ 144.3, 143.2, 137.7, 133.8, 132.2, 130.7, 129.5, 129.5, 128.6,128.2, 127.8, 127.1, 127.1, 127.0, 125.8, 123.3, 116.4, 111.7, 57.1,53.9, 43.0, 25.0, 22.2, 21.5. Anal. Calcd for C ₂₆H₂₆N₂O₂S: C, 72.53; H,6.09; N, 6.51. Found: C, 72.55; H, 6.11; N, 6.50.

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (2 ml) andindole (117 mg, 1.0 mmol) were added and the solution heated to refluxfor 11 hours. The reaction mixture was then concentrated andchromatographed to give 13 (75 mg, 91%) a white-solid. mp 132-135° C.;¹H NMR (400 MHz, CDCl₃) δ 7.84 (1H, s), 7.70-7.64 (3H, m), 7.24-7.07(7H, m), 6.95-6.89 (1H, m), 6.65 (1H, d, J=9.7 Hz), 6.57 (1H, d, J=2.4Hz), 6.50 (1H, d, J=7.5 Hz), 6.09 (1H, dd, J=5.1, 9.5 Hz), 4.99 (1H, d,J=7.7 Hz), 4.54 (1H, dd, J=2.9, 7.7 Hz), 4.26-4.22 (1H, m), 2.38 (3H,s); ¹³C NMR (4001 MHz, CDCl₃) δ 143.2, 136.5, 132.4, 132.2, 132.2,129.5, 128.9, 128.7, 128.6, 127.7, 127.1, 127.0, 126.4, 126.3, 122.5,122.0, 119.5, 119.0, 112.2, 111.2, 56.0, 38.8, 21.5. HRMS calcd forC₂₅H₂₂N₂O₂S (M⁺): 414.1402. Found: 414.1407.

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (2 ml) was thenadded followed by triethylamine hydrochloride (138 mg, 1.0 mmol) andpyrrolidine (83 μl, 1.0 mmol). The resulting heterogeneous mixture washeated to reflux for 14 hours. Upon completion, the reaction mixture wasconcentrated and chromatographed to give 14 (70 mg, 96%) a white solid.The regiochemistry and relative stereochemistry was proven by X-raydiffraction. ¹H NMR (400 MHz, CDCl₃) δ 7.74 (2H, d, J=8.3 Hz), 7.30 (2H,d, J=8.2 Hz), 7.22-7.17 (1H, m), 7.08-7.02 (2H, m), 6.84 (1H, d, J=7.5Hz), 6.61 (1H, d, J=9.7 Hz), 5.93 (1H, dd, J=4.9, 9.7 Hz), 4.70 (1H, brs), 4.45 (1H, d, J=3.7 Hz), 3.89 (1H, dd, J=4.2, 4.2 Hz), 2.58-2.49 (2H,m), 2.45 (3H, s), 2.36-2.29 (2H, m), 1.63-1.58 (4H, m); Anal. Calcd forC₂₁H₂₄N₂O₂S: C, 68.45; H, 6.56; N, 7.60. Found: C, 68.51; H, 6.62; N,7.55.

To a round bottomed flask was added 4 (66 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (2 ml) was thenadded followed by triethylamine hydrochloride (138 mg, 1.0 mmol) andpyrrolidine (83 μl, 1.0 mmol). The resulting heterogeneous mixture washeated to reflux for 16 hours. Upon completion, the reaction mixture wasconcentrated and chromatographed to-give 15 (67 mg, 84%) a white solid.mp 142-145° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.30 (2H, d, J=8.8 Hz), 7.99(2H, d, J=8.8 Hz), 7.24-7.18 (1H, m), 7.10-7.04 (2H, m), 6.95-6.90 (1H,m), 6.63 (1H, d, J=9.9 Hz), 5.93 (1H, dd, J=4.7, 9.7 Hz), 5.20-4.80 (1H,br s), 4.60 (1H, d, J=3.8 Hz), 3.40-3.35 (1H, m), 2.58-2.50 (2H, m),2.43-2.34 (2H, m), 1.64-1.57 (4H, m); ¹³C NMR (400 MHz, CDCl₃) δ 149.8,147.1, 132.8, 131.9, 129.7, 128.8, 128.2, 128.1, 128.0, 127.1, 125.0,124.1, 61.4, 54.4, 50.0, 23.4. Anal. Calcd for C₂₀H₂₁N₃O₄S: C, 60.13; H,5.30; N, 10.52. Found: C, 60.16; H, 5.33; N, 10.50.

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (2 ml) was thenadded followed by triethylamine (140 μl, 1.0 mmol) and piperidinehydrochloride (121 mg, 1.0 mmol). The resulting heterogeneous mixturewas heated to reflux for 14 hours. Upon completion, the reaction mixturewas concentrated and chromatographed to give 16 (72 mg, 94%) a whitesolid. mp 116-117° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.75 (2H, d, J=8.2 Hz),7.30 (2H, d, J=7.8 Hz), 7.21-7.18 (1H, m), 7.10-7.05 (1H, m), 7.04 (1H,d, J=7.5 Hz), 6.94 (1H, d, J=7.5 Hz), 6.61 (1H, dd, J=1.0, 9.7 Hz), 5.91(1H, dd, J=4.8, 9.7 Hz), 4.82 (1H, s (br)), 4.53 (1H, d, J=4.4 Hz),3.38-3.35 (1H, m), 2.44 (3H, s), 2.41-2.34 (2H, m), 2.16-2.09 (2H, m),1.40-1.26 (6H, m); ¹³C NMR (400 MHz, CDCl₃) δ 143.3, 137.7, 134.2,132.2, 129.6, 129.4, 128.2, 128.0, 127.7, 127.2, 126.6, 125.0, 64.2,50.9, 49.6, 26.2, 24.3, 21.5. HRMS calcd for C₂₂H₂₆N₂O₂S (M⁺): 382.1715.Found: 382.1713.

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (2 ml) was thenadded followed by triethylamine hydrochloride (138 mg., 1.0 mmol) andtetrahydroisoquinoline (125 μl, 1.0 mmol). The resulting heterogeneousmixture was heated to reflux for 15 hours. Upon completion, the reactionmixture was concentrated and chromatographed to give 17 (70 mg, 81%) awhite solid. mp 142-146° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.73 (2H, d,J=8.2 Hz), 7.26-7.18 (3H, m), 7.12-6.98 (5H, m), 6.90 (1H, d, J=8.1 Hz),6.80 (1H, d, J=6.8 Hz), 6.67 (1H, d, J=9.7 Hz), 5.95 (1H, dd, J=4.7, 9.7Hz), 4.80 (1H, s), 4.62 (1H, s), 3.68 (1H, AB, d, J=15.0 Hz), 3.63 (1H,dd, J=4.5, 4.5 Hz), 3.40 (1H, AB, d, J=15.0 Hz), 2.68-2.56 (4H, m), 2.40(3H, s); ¹³C NMR (400 MHz, CDCl₃) δ 143.4, 137.7, 137.7, 134.1, 133.8,132.2, 129.9, 129.6, 128.6, 128.5, 128.3, 127.9, 127.2, 126.8, 126.5,125.9, 125.4, 124.6. Anal. Calcd for C₂₆H₂₆N₂O₂S: C, 72.53; H, 6.09; N,6.51. Found: C, 72.56; H, 6.12; N, 6.50.

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (1 ml) was thenadded followed by triethylamine hydrochloride (138 mg, 1.0 mmol) andpotassium acetate (98 mg, 1.0 mmol). The resulting heterogeneous mixturewas heated to reflux for 15 hours. Upon completion, the reaction mixturewas concentrated and chromatographed to give 18 (63 mg, 88%) a whitesolid. ¹H NMR (400 MHz, CDCl₃) δ 7.77 (2H, d, J=8.3 Hz), 7.31(2H, d,J=8.2 Hz), 7.27-7.22 (1H, m), 7.19-7.07 (3H, m), 6.54 (1H, d, J=10.2Hz), 5.88 (1H, dd, J=3.7, 10.2 Hz), 5.48-5.44 (1H, m), 4.90 (1H, d,J=8.4 Hz), 4.74-4.69 (1H, m), 2.44 (3H, s), 1.78 (3H, s); ¹³C NMR (400MHz, CDCl₃) δ 170.6, 143.4, 138.2, 132.8, 131.9, 130.3, 129.7, 128.7,128.5, 127.4, 127.1, 127.1, 125.0, 71.0, 55.7, 21.5, 20.7. Anal. Calcdfor C₁₉H₁₉NO₄S: C, 63.85; H, 5.36; N, 3.92. Found: C, 63.88; H, 5.40; N,3.81.

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (1 ml) was thenadded followed by triethylamine (140 μl, 1.0 mmol) and benzoic acid (122mg, 1.0 mmol). The resulting homogeneous solution was heated to refluxfor 15 hours. Upon completion, the reaction mixture was concentrated andchromatographed to give 19 (73 mg, 87%) a white solid. mp 158-162° C.;¹H NMR (400 MHz, CDCl₃) δ 7.77 (2H, d, J=7.1 Hz), 7.65 (2H, d, J=8.3Hz), 7.56-7.50 (1H, m), 7.40-7.32 (3H, m), 7.30-7.22 (2H, m), 7.11 (1H,dd, J=1.3, 7.2 Hz), 6.98 (2H, d, J=8.1 Hz), 6.56 (1H, dd, J=1.3, 9.9Hz), 5.93 (1H, dd, J=3.3, 9.7 Hz), 5.79 (1H, ddd, J=1.7, 3.3, 9.2 Hz),5.12 (1H, d, J=8.4 Hz), 4.90 (1H, dd, J=8.8, 8.8 Hz), 2.19 (3H, s); ¹³CNMR (400 MHz, CDCl₃) δ 166.4, 143.3, 138.0, 133.4, 133.3, 132.3, 130.4,130.0, 129.7, 128.8, 128.8, 128.3, 127.5, 127.2, 126.9, 125.7, 72.3,56.8, 21.6. HRMS calcd for C₂₄H₂₁NO₄S (M⁺): 419.1191. Found: 419.1997.

To a round bottomed flask was added 3 (60 mg, 0.2 mmol), [Rh(COD)Cl]₂(2.5 mg, 0.005 mmol), and DPPF (5.5 mg, 0.01 mmol). THF (1 ml) was thenadded followed by triethylamine (140 μl, 1.0 mmol) and pivalic acid (102mg, 1.0 mmol). The resulting homogeneous solution was heated to refluxfor 15 hours. Upon completion, the reaction mixture was concentrated andchromatographed to give 20 (61 mg, 77%) a white solid. ¹H NMR (400 MHz,CDCl₃) δ 7.75 (2H, d, J=8.0 Hz), 7.28 (2H, d, J=8.0 Hz), 7.16-7.00 (3H,m), 6.85 (1H, d, J=7.6 Hz), 6.55 (1H, d, J=9.7 Hz), 5.91 (1H, dd, J=4.1,9.7 Hz), 5.34 (1H, dd, J=5.9, 5.9 Hz), 4.98 (1H, d, J=8.4 Hz), 4.70 (1H,dd, J=7.3, 7.3 Hz), 2.42 (3H, s), 1.07 (9H, s). HRMS calcd forC₂₂H₂₅NO₄S (M⁺): 399.1504. Found: 399.1507.

To a round bottomed flask was added 21 (100 mg, 0.27 mmol) and potassiumcarbonate (112 mg. 0.81 mmol). Acetone (3 ml) was then added followed byiodomethane (18 μl, 0.28 mmol). The mixture was stirred at roomtemperature for 4 hours then quenched with water. Extraction withethylacetate, combining of the organic fractions and concentration gavea light yellow solid. Chromatography gave pure 21 (101 mg, 98%) a whitecrystalline solid. mp 109-111° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.86 (2H,d, J=8.0 Hz), 7.31 (2H, d, J=8.0 Hz), 7.26-7.12 (3H, m), 7.06 (1H, d,J=6.9 Hz), 6:58 (1H, d; J=9.7 Hz), 5.95 (1H, dd, J=4.6, 9.9 Hz), 5.35(1H, d, J=4.5 Hz), 3.42 (1H, dd, J=4.5, 4.5 Hz), 2.62-2.48 (4H, m), 2.50(3H, s), 2.45 (3H, s), 1.70-1.63 (4H, m); ¹³C NMR (400 MHz, CDCl₃) δ143.0, 137.7, 133.6, 132.1, 129.5, 129.1, 128.9, 128.2, 128.1, 127.4,126.5, 125.9, 58.2, 56.5, 48.6, 29.6, 23.5, 21.5. Anal. Calcd forC₂₂H₂₆N₂O₂S: C, 69.08; H, 6.85; N, 7.32. Found: C, 69.14; H, 6.91; N,7.30.

To a round bottomed flask was added 21 (100 mg, 0.26 mmol), ethylacetate(2 ml) and palladium on carbon (5 mg). Hydrogen was added over thisheterogeneous mixture via balloon for 15 hours. Upon completion, themixture was filtred through celite and concentrated to give 22 a whitesolid. Crude ¹H NMR showed that this crude product was >95% pure.Further purification could be obtained by chromatography giving pure 22(98 mg, 98%). mp 109-110° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.99 (2H, d, J=S8.1 Hz), 7.30 (2H, d, J=8.3 Hz), 7.15-7.02 (4H, m), 5.29 (1H, d, J=8.1Hz), 3.03-2.67 (5H, m), 2.65-2.52 (2H, m), 2.44 (3H, s), 2.43 (3H, s),2.05-1.96 (1H, m), 1.90-1.80 (1H, m), 1.72-1.64 (4H, m); ¹³C NMR (400MHz, CDCl₃) δ 142.8, 138.5, 137.5, 133.9, 129.2, 128.5, 127.7, 127.1,126.4, 60.0, 59.3, 48.7, 30.3, 27.9, 23.6, 21.5, 21.4l . Anal. Calcd forC₂₂H₂₈N₂O₂S: C, 68.72; H, 7.34; N, 7.29. Found: C, 68.79; H, 7.37; N,7.22.

To a quartz tube was added 22 (80 mg, 0.2 mmol), 1,4-dimethoxybenzene(110 mg, 0.8 mmol) and sodium borohydride (76 mg, 2.0 mmol) followed by90% aqueous ethanol solution (3 ml). The mixture was irradiated at 254nm in a rayonet reactor for 2.5 hours. The crude mixture wasconcentrated azeotropically with ethanol and then chromatographed (90%acetone, 9% MeOH, 1% triethylamine) to give 23 (42 mg, 91%). Spectraldata was identical to the literature data.

To a round bottomed flask was added 16 (100 mg, 0.25 mmol) and potassiumcarbonate (112 mg, 0.81 mmol). Acetone (3 ml) was then added followed byiodomethane (18 μl, 0.28 mmol). The mixture was stirred at roomtemperature for 4 hours then quenched with water. Extraction withethylacetate, combining of the organic fractions and concentration gavea light yellow solid. Chromatography gave pure 24 (101 mg, 98%) a whitecrystalline solid. mp 139-141° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.35 (2H,d, J=8.8 Hz), 8.22 (2H, d, J=8.8 Hz), 7.28-7.22 (3H, m), 7.09 (1H, d,J=6.2 Hz), 6.60 (1H, d, J=9.9 Hz), 5.95 (1H, dd, J=4.0, 9.9 Hz), 5.43(1H, d, J=6.6 Hz), 3.54-3.49 (1H, m), 2.62 (3H, s), 2.60-2.54 (4H, m),1.72-1.66 (4H, m); ¹³C NMR (400 MHz, CDCl₃) δ 149.8, 146.6, 133.6,131.6, 129.5, 128.6, 128.3, 128.0, 126.8, 125.3, 124.0, 58.4, 58.0,48.5, 29.8, 23.7. Anal. Calcd for C₂₁H₂₃N₃O₄S: C, 61.00; H, 5.61; N,10.16. Found: C, 61.11; H, 5.65; N, 10.12.

To a round bottomed flask was added 18 (70 mg, 0.20 mmol) and potassiumcarbonate (110 mg, 0.80 mmol). Acetone (2.5 ml) was then added followedby iodomethane (15 μl, 0.24 mmol). The mixture was stirred at roomtemperature for 4 hours then quenched with water. Extraction withethylacetate, combining of the organic fractions and concentration gavea light yellow solid. Chromatography gave pure 25 (67 mg, 91%) a whitecrystalline solid. mp 113-116° C.; ¹H NMR (400 MHz, CDCl₃) δ 7.78 (2H,d, J=8.2 Hz), 7.32 (2H, d, J=8.2 Hz), 7.25-7.17 (2H, m), 7.13-6.98 (2H,m),6.46 (1H, dd, J=1.8, 9.9 Hz), 5.85 (1H, dd, J=2.9, 9.9 Hz), 5.71 (1H,ddd, J=2.0, 2.6, 10.1 Hz), 5.60 (1H, d, J=10.1 Hz),2.69(3H, s),2.44(3H,s), 1.90(3H, s); ¹³C NMR (400 MHz, CDCl₃) δ 170.2, 143.4, 137.3, 133.2,131.4, 129.6, 129.2, 128.4, 128.3, 127.1, 126.7, 126.4, 69.7, 60.0,29.5, 21.4, 20.8. Anal. Calcd for C₂₀H₂₁NO₄S: C, 64.67; H, 5.70; N,3.77. Found: C, 64.75; H, 5.77; N, 3.72.

Abbreviations

ee “enantiomerically enriched,” or “enantiomeric enrichment” THFtetrahydrofuran DPPE 1,2-bis(diphenylphosphino)ethane BINAP2,2′-bis(diphenylphosphino)-1,1′-binaphthyl

What is claimed is:
 1. A compound according to formula IV:

wherein: a) R₈ is H or CH_(3;) b) t=0-3 c) R₉ is a C₃-C₆ aryl optionallysubstituted at one or more positions with a group selected from: a C₁-C₃alkyl; a C₁-C₃ alkoxy; Cl; F; NO₂; and CF_(3;) d) X and Y areindependently selected from the group consisting of H; NH₂; F; Cl; Br; aC₁-C₃ alkyl; and a C₁-C₃ alkoxy; or wherein the combination XY or YYtogether form a C₃-C₆ carbocyclic ring or a C₃-C₆ heterocyclic ringcontaining one or more heteroatoms selected from the group consisting ofO; N; and S; e) Z is selected from O or NR_(a), wherein R_(a) isselected from: (i) a straight or branched C₁-C₆ alkyl; (ii) phenyl;(iii) (O)C—O—R_(b), wherein R_(b) is a straight or branched C₁-C₆ alkyl;(iv) —SO₂—R_(c), wherein R_(c) is an unsubstituted phenyl or a phenylsubstituted with a C₁-C₃ alkyl or NO₂; and (v) —SO₂—(CH₂)_(q)—Si(CH₃)₃wherein q is 1-3; and with the proviso that when Z is O, R₁₀ is H; whenZ is NR_(a), R₁₀ is either H or CH₃; and with the further proviso thatwhen Z is O and R₁₀ is H, t is 2 or 3 and either X or Y is not H.
 2. Thecompound of claim 1, wherein R₈ is H.
 3. The compound of claim 1,wherein X=H and Y=H.
 4. A compound selected from the group consistingof: (1S,2S)-N-(1-hydroxyl-1,2-dihydro-naphthalen-2-yl)-benzenesulfonamide;(1R,2R)-2-(methyl-phenyl-amino)-1,2-dihydro-naphthalen-1-ol;(1R*,2R*)-2-benzylamino-1,2-dihydro-naphthalen-1-ol; (1R*,2R*)-2-(4-methoxy-benzylamino)-1,2-dihydro-naphthalen-1-ol;(1R,2S)-2-methoxy-N-phenyl-1,2-dihydro-1-naphthalenamine;tert-butyl(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenylcarbamate;N-[(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenyl]-2-(trimethylsilyl)ethanesulfonamide;N-[(1R,2S)-2-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl]-4-methylbenzenesulfonamide;N-[(1R,2S)-2-methoxy-1,2,3,4-tetrahydro-1-naphthalenyl]-4-methylbenzenesulfonamide;4-methyl-N-[(1R,2S)-2-phenoxy-1,2,3,4-tetrahydro-1-naphthalenyl]benzenesulfonamide;(1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2,3,4-tetrahydro-2-naphthalenylacetate;(1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2-dihydro-2-naphthalenylbenzoate;(1R,2S)-1-{[(4-methylphenyl)sulfonyl]amino}-1,2-dihydro-2-naphthalenylpivalate;N-[(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenyl]-2-(trimethylsilyl)ethanesulfonamide, andtert-butyl(1R,2S)-2-methoxy-1,2-dihydro-1-naphthalenylcarbamate.
 5. Apharmaceutical composition comprising a compound according to formulaIV:

wherein: a) R₈ is H or CH₃; b) t=0-3 c) R₉ is a C₃-C₆ aryl optionallysubstituted at one or more positions with a group selected from: aC₁--C₃ alkyl; a C₁-C₃ alkoxy; Cl; F; NO₂; and CF₃; d) X and Y areindependently selected from the group consisting of H; NH₂; F; Cl; Br; aC₁-C₃ alkyl; and a C₁-C₃ alkoxy; or wherein the combination XY or YYtogether form a C₃-C₆ carbocyclic ring or a C₃-C₆ heterocyclic ringcontaining one or more heteroatoms selected from the group consisting ofO; N; and S; e) Z is selected from O or NR_(a), wherein R_(a) isselected from: (i) a straight or branched C₁-C₆ alkyl; (ii) phenyl;(iii) (O)C—O—R_(b), wherein R_(b) is a straight or branched C₁-C₆ alkyl;(iv) —SO₂—R_(c), wherein R_(c) is an unsubstituted phenyl or a phenylsubstituted with a C₁-C₃ alkyl or NO₂; and (v) —SO—(CH₂)_(q)—Si(CH₃)₃wherein q is 1-3; and when Z is O, R₁₀ is H; when Z is NR_(a); R₁₀ iseither H or CH₃.
 6. A pharmaceutical composition comprising a compoundaccording to claim
 4. 7. A method of treating a patient for pain,comprising administering to said patient an effective amount of thepharmaceutical compound of claim
 5. 8. A method of treating a patientfor Parkinson's disease, comprising administering an effective amount ofthe pharmaceutical composition of claim
 5. 9. A method of treating apatient for cancer, comprising administering an effective amount of thepharmaceutical compound of claim
 5. 10. A method of treating a patientfor AIDS, comprising administering an effective amount of thepharmaceutical compound of claim
 5. 11. A method of treating a patientfor pain, comprising administering to said patient an effective amountof the pharmaceutical composition of claim
 6. 12. A method of treating apatient for Parkinson's Disease, comprising administering to saidpatient an effective amount of the pharmaceutical composition of claim6.
 13. A method of treating a patient for cancer, comprisingadministering to said patient an effective amount of the pharmaceuticalcomposition of claim
 6. 14. A method of treating a patient for AIDS,comprising administering to said patient an effective amount of thepharmaceutical composition of claim
 6. 15. A process for preparing acompound of formula IV:

wherein: a) R₈ is H or CH₃; b) t=0-3 c) R₉ is a C₃-C₆ aryl optionallysubstituted at one or more positions with a group selected from: a C₁-C₃alkyl; a C₁-C₃ alkoxy; Cl; F; NO₂; and CF_(3;) d) X and Y areindependently selected from the group consisting of H; NH₂; F; Cl; Br; aC₁-C₃ alkyl; and a C₁-C₃ alkoxy; or wherein the combination XY or YYtogether form a C₃-C₆ carbocyclic ring or a C₃-C₆ heterocyclic ringcontaining one or more heteroatoms selected from the group consisting ofO; N; and S; e) Z is selected from O or NR_(a) wherein R_(a) is selectedfrom: (i) a straight or branched C₁-C₆ alkyl; (ii) phenyl; (iii)(O)C—O—R_(b) wherein R_(b) is a straight or branched C₁-C₆ alkyl; (iv)—SO₂—R_(c) wherein R_(c) is an unsubstituted phenyl or a phenylsubstituted with a C₁-C₃ alkyl or NO₂; and (v) —SO₂—(CH₂)_(q)—Si(CH₃)₃wherein a is 1-3; and when Z is O, R₁₀ is H; when Z is NR_(a), R₁₀ iseither H or CH; comprising reacting a compound of formulaR₉—(CH₂)_(t)NHR₈ with a compound of formula V

wherein R₈, R₉, t, X, Y, and Z are as defined above and wherein saidreaction is catalyzed by [Rh(COD)Cl]₂ in the presence of a phosphineligand.
 16. The process of claim 15, wherein said phosphine ligand isselected from the group consisting of; DPPF; (R)-(S)-BPPFA; and(R)-(S)-PPF-P^(t)Bu₂.